Grey’s Anatomy: Every Main Character Who Was Killed Off (& Why)

Grey’s Anatomy has gained a reputation for killing some of its most beloved characters off with some incredibly emotional deaths, and even main characters aren't safe. Grey’s Anatomy follows the basic premise of medical dramas, focusing on the lives of surgical interns, residents, and attendings as they balance their professional and personal lives, which more often than not overlap and create a lot of drama inside and outside Seattle Grace Hospital (now Grey Sloan Memorial Hospital).

The show is led by Meredith Grey (Ellen Pompeo) alongside other main characters who became audience favorites, many lasting for several years through Grey's Anatomy's 20-season-plus run. Grey’s Anatomy has become infamous for killing characters when their time on the show is over, and only some lucky few have been given satisfying endings where they got to keep on living. Unfortunately, many of the main Grey's Anatomy characters who were killed off were long-term presences viewers had come to know and love over the years.

10 Denny Duquette Died After A Heart Transplant

Season 2, Episode 27 – "Losing My Religion"

Denny in a hospital bedwith Izzie in Grey's Anatomy

Denny looking sad in Grey's Anatomy

JDM as Denny smiling in the hospital bed in Grey's Anatomy

Denny in a hospital bedwith Izzie in Grey's Anatomy

Denny looking sad in Grey's Anatomy

JDM as Denny smiling in the hospital bed in Grey's Anatomy

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Denny in a hospital bedwith Izzie in Grey's Anatomy

Denny looking sad in Grey's Anatomy

JDM as Denny smiling in the hospital bed in Grey's Anatomy

Denny in a hospital bedwith Izzie in Grey's Anatomy

Denny looking sad in Grey's Anatomy

JDM as Denny smiling in the hospital bed in Grey's Anatomy

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Denny in a hospital bedwith Izzie in Grey's Anatomy

Denny looking sad in Grey's Anatomy

JDM as Denny smiling in the hospital bed in Grey's Anatomy

Denny in a hospital bedwith Izzie in Grey's Anatomy

Denny looking sad in Grey's Anatomy

JDM as Denny smiling in the hospital bed in Grey's Anatomy

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There were several deaths in the second season of Grey's Anatomy. However, the most tragic death that season was that of Denny Duquette, played by Jeffrey Dean Morgan. He was the first major recurring character to be killed off. While a patient on the show, he was also someone who spent a great deal of time at the hospital, and that resulted in him getting to know Izzie and the two fell in love. However, this also led to Izzie doing something morally questionable, and it ended up resulting in Denny's death.

Denny needed a heart transplant, and he was waiting for a donor. He and Izzie began dating, and she decided she wanted to help him get his new heart. Izzie cut his LVAD wire and made his heart look worse than it was. As a result, he shot up the transplant list and he got his heart. Sadly, just hours after getting his new heart, Denny had a stroke and died. Izzie had to live with this decision for the rest of her time on the show.

It's Izzie having to live with that decision that actually made Denny's death hit fans harder. Watching Izzie grieve Denny while finding out she had a brain tumor that was making her hallucinate him made the experience even more difficult.

9 Meredith's Parents Died On Grey's Anatomy

Season 3, Episode 17 – "Some Kind Of Miracle" & Season 15, Episode 11 – "The Winner Takes It All"

A split image of Thatcher and Ellis smiling in Grey's Anatomy.

Thatcher Grey laying in a hospital bed with Lexie comforting him and Alex standing to the side of the bed

Ellis and Meredith Grey talking and holding hands on Grey's Anatomy

A split image of Thatcher and Ellis smiling in Grey's Anatomy.

Thatcher Grey laying in a hospital bed with Lexie comforting him and Alex standing to the side of the bed

Ellis and Meredith Grey talking and holding hands on Grey's Anatomy

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A split image of Thatcher and Ellis smiling in Grey's Anatomy.

Thatcher Grey laying in a hospital bed with Lexie comforting him and Alex standing to the side of the bed

Ellis and Meredith Grey talking and holding hands on Grey's Anatomy

A split image of Thatcher and Ellis smiling in Grey's Anatomy.

Thatcher Grey laying in a hospital bed with Lexie comforting him and Alex standing to the side of the bed

Ellis and Meredith Grey talking and holding hands on Grey's Anatomy

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A split image of Thatcher and Ellis smiling in Grey's Anatomy.

Thatcher Grey laying in a hospital bed with Lexie comforting him and Alex standing to the side of the bed

Ellis and Meredith Grey talking and holding hands on Grey's Anatomy

A split image of Thatcher and Ellis smiling in Grey's Anatomy.

Thatcher Grey laying in a hospital bed with Lexie comforting him and Alex standing to the side of the bed

Ellis and Meredith Grey talking and holding hands on Grey's Anatomy

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The story of Grey's Anatomy initially had Meredith Grey as the main focus. While the show eventually became more of an ensemble affair, Meredith was still one of the most important members of the cast of characters. That means her home life was also part of the story, and she lost both of her parents throughout the series. Her mother, Ellis Grey (Kate Burton), was the first to die in season 3. She was a somewhat antagonistic presence in Grey's Anatomybut was still Meredith's mom, and when her battle with Alzheimer's led to her death, it was incredibly emotional.

Meredith's dad died many years later, with his death coming in Grey's Anatomy season 15. Thatcher Grey (Jeff Perry) also had a rough relationship with his daughter, and they never really had a chance to reconcile before it was too late. By the time Meredith got to know her sister, Lexie, she had finally started to mend the relationship with her dad. She then went to see him, and he died after a final conversation with his daughter.

Their deaths were seen as logical steps in growing up. Most children outlive their parents, and as Meredith aged, it would be natural for her parents to die even while she married, had children, and thrived. Their losses were emotional for the audience and critics because they were losses that helped Meredith to grow.

8 George O’Malley Died After Getting Hit By A Bus

Season 6, Episode 1 – "Good Mourning"

George O'Malley leaning against a window and looking at something in Grey's Anatomy

George O'Malley (T.R. Knight) tearing up in Grey's Anatomy.

George looking confused on Grey's Anatomy

George O'Malley leaning against a window and looking at something in Grey's Anatomy

George O'Malley (T.R. Knight) tearing up in Grey's Anatomy.

George looking confused on Grey's Anatomy

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George O'Malley leaning against a window and looking at something in Grey's Anatomy

George O'Malley (T.R. Knight) tearing up in Grey's Anatomy.

George looking confused on Grey's Anatomy

George O'Malley leaning against a window and looking at something in Grey's Anatomy

George O'Malley (T.R. Knight) tearing up in Grey's Anatomy.

George looking confused on Grey's Anatomy

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George O'Malley leaning against a window and looking at something in Grey's Anatomy

George O'Malley (T.R. Knight) tearing up in Grey's Anatomy.

George looking confused on Grey's Anatomy

George O'Malley leaning against a window and looking at something in Grey's Anatomy

George O'Malley (T.R. Knight) tearing up in Grey's Anatomy.

George looking confused on Grey's Anatomy

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George O’Malley's (T.R. Knight) demise was quite tragic. George struggled to find his path and when he seemed to have finally found it as a trauma surgeon, he suddenly decided to join the U.S. Army in Iraq. Richard Webber gave him the last day off, so he could spend time with his family, but on his way home, he jumped in front of a bus to save a woman’s life. George was left severely disfigured, to the point where the doctors couldn’t recognize him.

It wasn’t until he traced “007” on Meredith’s hand that they knew who they were trying to save. Unfortunately, George’s brain swelled during surgery, and he was declared brain-dead, becoming the first major character to die on Grey's Anatomy. Behind the scenes, Knight left Grey's Anatomy due to a “gradual breakdown of communication.” Rhimes reportedly discouraged him from coming out, and he wasn't comfortable with where George’s story was going. Knight did return as George in Grey's Anatomy season 17 during Meredith's hallucinations.

His death was the first to hit the audience the hardest. He was a character that was genuinely missed as he was a core member of the group of friends at the center of the show.

7 Reed Adamson, Dr. Charles Percy, Mary Portman Died In A Hospital Shooting

Season 6, Episodes 23-24 – "Sanctuary" & "Death And All His Friends"

Alex receiving CPR after being shot in Grey's Anatomy

Callie and Arizon with a nurse and patient in the episode Sanctuary of Grey's Anatomy

Bailey with another doctor and a patient in the episode Sanctuary of Grey's Anatomy

Alex receiving CPR after being shot in Grey's Anatomy

Callie and Arizon with a nurse and patient in the episode Sanctuary of Grey's Anatomy

Bailey with another doctor and a patient in the episode Sanctuary of Grey's Anatomy

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Alex receiving CPR after being shot in Grey's Anatomy

Callie and Arizon with a nurse and patient in the episode Sanctuary of Grey's Anatomy

Bailey with another doctor and a patient in the episode Sanctuary of Grey's Anatomy

Alex receiving CPR after being shot in Grey's Anatomy

Callie and Arizon with a nurse and patient in the episode Sanctuary of Grey's Anatomy

Bailey with another doctor and a patient in the episode Sanctuary of Grey's Anatomy

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Alex receiving CPR after being shot in Grey's Anatomy

Callie and Arizon with a nurse and patient in the episode Sanctuary of Grey's Anatomy

Bailey with another doctor and a patient in the episode Sanctuary of Grey's Anatomy

Alex receiving CPR after being shot in Grey's Anatomy

Callie and Arizon with a nurse and patient in the episode Sanctuary of Grey's Anatomy

Bailey with another doctor and a patient in the episode Sanctuary of Grey's Anatomy

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Since Grey's Anatomy is a melodrama, many things happened at the hospital that seemed excessive. This included the two-parter finale of Grey's Anatomy season 6 that ended up as the highest-rated episode for the series. The episodes "Sanctuary" and "Death And All His Friends" focused on an active shooter situation in the hospital. Reed Adamson is fatally shot, followed promptly by Alex Karev (Justin Chamers), though he's only wounded. Charles Percy (Robert Baker) also takes a bullet, dying in the second episode of the two-parter.

What some fans might not remember is that Mandy Moore was on Grey's Anatomy as a character named Mary Portman, and this was the episode she guest starred in. Mary is a woman who needs a colostomy reversal and needs a blood transfusion. Sadly, a man named Gary Clark went on the shooting spree. He finds the room they are in, and he fatally shoots Dr. Percy. Mary ends up returning to the hospital for her surgery later, but dies during the procedure.

The season six finale of the series was lauded for its acting and writing. Entertainment Weekly said of the episode:

They did a bang-up job, it felt real in every way, thanks to some stellar performances and writing. And yet it maintained its Grey's-ness thanks to some quieter moments and plenty of witty exchanges to boot.

The deaths that actually took place in the episode were largely glossed over by critics and fans in favor of paying attention to the emotional storylines for Meredith, Christina, and Bailey that played out. The acting of the series regulars who survived the shooting were the ones that critics and fans alike remembered. At the time, Meredith's plea for the shooter to shoot her was lauded as the best scene of the series so far.

6 Henry Burton Died Due To A Heart Tumor

Season 8, Episode 10 – "Suddenly"

Henry Burton in a hospital bed in Grey's Anatomy

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

Henry Burton in a hospital bed in Grey's Anatomy

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

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Henry Burton in a hospital bed in Grey's Anatomy

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

Henry Burton in a hospital bed in Grey's Anatomy

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

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Henry Burton in a hospital bed in Grey's Anatomy

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

Henry Burton in a hospital bed in Grey's Anatomy

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Scott Foley As Henry Burton Sitting In Hospital Bed In Grey's Anatomy.jpg

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Scott Foley starred in Grey's Anatomy as Henry Burton. He needed a heart transplant, but he had no insurance. This caused one of the more controversial storylines on the show, as Dr. Teddy Altman married Henry. It wasn't because she loved him, but it was because she knew he could use her health insurance. While this could cause problems later if insurance fraud was detected, the two ended up falling in love and they became a real couple.

This made things heartbreaking when he ended up being rushed into surgery later. Dr. Cristina Yang ended up performing the surgery to try to save his life, but she couldn't, and Henry ended up dying. This was especially heartbreaking as the episode showed Teddy in the morgue breaking down over his body, as she lost him just as she began to love him. This was a case of a storyline just playing out as planned in advance, as Henry was never expected to be a long-term character.

5 Lexie Grey Died In A Plane Crash

Season 8, Episode 24 – "Flight"

Lexie Grey looking on in Grey's Anatomy

Lexie Grey working in Grey's Anatomy

Lexie Grey smiling in Grey's Anatomy

Lexie Grey looking on in Grey's Anatomy

Lexie Grey working in Grey's Anatomy

Lexie Grey smiling in Grey's Anatomy

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Lexie Grey looking on in Grey's Anatomy

Lexie Grey working in Grey's Anatomy

Lexie Grey smiling in Grey's Anatomy

Lexie Grey looking on in Grey's Anatomy

Lexie Grey working in Grey's Anatomy

Lexie Grey smiling in Grey's Anatomy

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Lexie Grey looking on in Grey's Anatomy

Lexie Grey working in Grey's Anatomy

Lexie Grey smiling in Grey's Anatomy

Lexie Grey looking on in Grey's Anatomy

Lexie Grey working in Grey's Anatomy

Lexie Grey smiling in Grey's Anatomy

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Meredith's half-sister, Lexie Grey (Chyler Leigh) died during one of the most traumatic events in the series. In season 8, Meredith, Derek Shepherd, Cristina Yang, Mark Sloan, Arizona Robbins, and Lexie were on their way to assist with the surgery of conjoined twins at a hospital in Boise when their plane crashed.

However, there was enough time for Mark to say goodbye to her, and he stayed by her side until her last breath, assuring her he loved her. Unlike other cases where the decision was based on behind-the-scenes conflict, Leigh’s exit from Grey's Anatomy was because she decided it was time to close Lexie’s arc and spend more time with her family. Like George O'Malley, Lexie also reappeared in Grey's Anatomy season 17 for Meredith's coma hallucinations to remind Meredith that she's allowed to enjoy her life.

While fans were heartbroken about the death of Lexie, so was Shonda Rhimes, who released a statement about saying goodbye to the character:

This finale was incredibly hard to write. I did not enjoy it. It made me sick and it made me sad. We end the season not knowing ANYTHING about the future. Except for two things. We know we are definitely saying goodbye to two of my favorite people: Chyler Leigh (Lexie) and Kim Raver (Teddy).

I love Chyler and I love the character of Lexie Grey. She was an important member of my 'Grey's' family. This was not an easy decision. But it was a decision that Chyler and I came to together. We had a lot of thoughtful discussion about it and ultimately we both decided this was the right time for her character's journey to end. As far as I'm concerned Chyler will always remain a part of the Shondaland family and I can't wait to work with her again in the future.

 

4 Mark Sloan Died In A Plane Crash

Season 9, Episode 2 – "Remember The Time"

Mark Sloan leans forward in his doctor's coat in Grey's Anatomy

Jackson and Mark in Grey's Anatomy

Mark with his daughter Sloan and an annoyed Lexie in Grey's Anatomy

Mark Sloan leans forward in his doctor's coat in Grey's Anatomy

Jackson and Mark in Grey's Anatomy

Mark with his daughter Sloan and an annoyed Lexie in Grey's Anatomy

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Mark Sloan leans forward in his doctor's coat in Grey's Anatomy

Jackson and Mark in Grey's Anatomy

Mark with his daughter Sloan and an annoyed Lexie in Grey's Anatomy

Mark Sloan leans forward in his doctor's coat in Grey's Anatomy

Jackson and Mark in Grey's Anatomy

Mark with his daughter Sloan and an annoyed Lexie in Grey's Anatomy

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Mark Sloan leans forward in his doctor's coat in Grey's Anatomy

Jackson and Mark in Grey's Anatomy

Mark with his daughter Sloan and an annoyed Lexie in Grey's Anatomy

Mark Sloan leans forward in his doctor's coat in Grey's Anatomy

Jackson and Mark in Grey's Anatomy

Mark with his daughter Sloan and an annoyed Lexie in Grey's Anatomy

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Another character who dies in Grey's Anatomy as a consequence of the infamous plane crash is Mark Sloan (Eric Dane). With the help of Cristina, who realized he had a cardiac tamponade and drained the fluid, Mark was able to survive until they were rescued, but his health continued to deteriorate. It was later revealed in Grey’s Anatomyseason 9 premiere episode that Mark was on life support, and as determined by his will, the machines were turned off.

Mark died with Derek and Callie Torres (Sandra Ramirez) by his side. As for why Eric Dane left Grey’s Anatomy, he revealed he saw an opportunity to leave the show as he was already interested in other projects. Dane did reprise the role of Mark in Grey's Anatomy season 17 when he appears in Meredith's "dreams" and lets her know that he's always watching over Callie, Arizona, and his daughter.

Mark's death had a huge impact on the show and the audience. That's because the audience got to experience all sides of Mark Sloane. They saw him grow from a man who had betrayed his best friend by having an affair with his wife to someone who had built a family at the hospital and started changing his ways. The audience was truly heartbroken by his death.

3 Samuel Norbert Avery Died At Birth

Season 11, Episode 11 – "All I Could Do Was Cry"

Jackson & April With Baby Samuel In Grey's Anatomy.jpg

Jackson Avery & April Kepner With Baby Samuel In Grey's Anatomy.

Jesse Williams As Jackson Avery And Sarah Drew As April Kepner In Grey's Anatomy.jpg

Jackson & April With Baby Samuel In Grey's Anatomy.jpg

Jackson Avery & April Kepner With Baby Samuel In Grey's Anatomy.

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Jackson & April With Baby Samuel In Grey's Anatomy.jpg

Jackson Avery & April Kepner With Baby Samuel In Grey's Anatomy.

Jesse Williams As Jackson Avery And Sarah Drew As April Kepner In Grey's Anatomy.jpg

Jackson & April With Baby Samuel In Grey's Anatomy.jpg

Jackson Avery & April Kepner With Baby Samuel In Grey's Anatomy.

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Jackson & April With Baby Samuel In Grey's Anatomy.jpg

Jackson Avery & April Kepner With Baby Samuel In Grey's Anatomy.

Jesse Williams As Jackson Avery And Sarah Drew As April Kepner In Grey's Anatomy.jpg

Jackson & April With Baby Samuel In Grey's Anatomy.jpg

Jackson Avery & April Kepner With Baby Samuel In Grey's Anatomy.

Jesse Williams As Jackson Avery And Sarah Drew As April Kepner In Grey's Anatomy.jpg

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One of the saddest episodes on Grey's Anatomy came in season 11. This death in Grey's was not to a long-standing cast member. Instead, this death was of the baby of two mainstays on the show. While they had many ups and downs, Jackson (Jesse Williams) and April (Sarah Drew) had one of the best love stories on the show. They ended up pregnant with their child, but then tragedy struck. They learned the unborn baby had a rare disease that caused his bones to break while in the womb.

Jackson and April knew that this was causing great pain to the baby, and they chose to deliver the baby 24 weeks into the pregnancy as a result. Samuel Norbert Avery was born prematurely, and his parents were able to hold him for a matter of minutes before he died. In fiction, as in real life, the deaths of children hits especially hard because these are people who haven't had a chance to live. The death of Samuel also affected Jackson and April's relationship going forward, so the audience couldn't forget it.

Sarah Drew, who plays April, pitched the story as she was pregnant at the time in real life. The actor later said that she felt guilty about it because she went into labor after shooting the scene and her real baby spent 11 days in the NICU.

2 Derek Shepherd Died After A Car Accident

Season 11, Episode 21 – "How To Save A Life"

Derek Shepherd in a coma on his deathbed in Grey's Anatomy

Derek leaning against a wall in Grey's Anatomy

Addison and Derek in Grey's Anatomy

Derek Shepherd in a coma on his deathbed in Grey's Anatomy

Derek leaning against a wall in Grey's Anatomy

Addison and Derek in Grey's Anatomy

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Derek Shepherd in a coma on his deathbed in Grey's Anatomy

Derek leaning against a wall in Grey's Anatomy

Addison and Derek in Grey's Anatomy

Derek Shepherd in a coma on his deathbed in Grey's Anatomy

Derek leaning against a wall in Grey's Anatomy

Addison and Derek in Grey's Anatomy

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Derek Shepherd in a coma on his deathbed in Grey's Anatomy

Derek leaning against a wall in Grey's Anatomy

Addison and Derek in Grey's Anatomy

Derek Shepherd in a coma on his deathbed in Grey's Anatomy

Derek leaning against a wall in Grey's Anatomy

Addison and Derek in Grey's Anatomy

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One of the saddest and also most criticized Grey's Anatomy deaths is Derek Shepherd’s (Patrick Dempsey). Meredith and Derek were the show’s main couple, but that came to an end in season 11 when Derek died and left not only Meredith but also many viewers with a broken heart. After a lot of troubles in their marriage, Derek decided to move to Seattle from DC to be with his family, but he had to briefly return to resign. On his way there, he got into a car accident, and after a lot of complications, he couldn’t be saved.

Meredith made the hard decision of removing him from life support. The reasons behind Dempsey’s departure from Grey's Anatomy are a combination of him feeling it was time for him to leave and on-set conflicts with creator Shonda Rhimes, Pompeo, and the rest of the cast. Nevertheless, Derek is one of the many characters who die in Grey's Anatomy to receive a special cameo in season 17. Appearing in three installments, he sees Meredith on the beach during her dream, and the two talk about their family.

His death hit the audience particularly hard because the audience was able to see it from his point of view. That's not something that happens in the series. Derek narrated the events surrounding his death, despite being unable to communicate with the doctors who were unable to help him. It made the entire sequence even more tragic.

1 Andrew DeLuca Died When Someone Stabbed Him

Season 17, Episode 7 – "Helplessly Hoping"

An image of Andrew DeLuca leaning against a wall in Grey's Anatomy

DeLuca in the hospital on Grey's Anatomy

DeLuca argues with Meredith in the hospital corridors

An image of Andrew DeLuca leaning against a wall in Grey's Anatomy

DeLuca in the hospital on Grey's Anatomy

DeLuca argues with Meredith in the hospital corridors

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An image of Andrew DeLuca leaning against a wall in Grey's Anatomy

DeLuca in the hospital on Grey's Anatomy

DeLuca argues with Meredith in the hospital corridors

An image of Andrew DeLuca leaning against a wall in Grey's Anatomy

DeLuca in the hospital on Grey's Anatomy

DeLuca argues with Meredith in the hospital corridors

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An image of Andrew DeLuca leaning against a wall in Grey's Anatomy

DeLuca in the hospital on Grey's Anatomy

DeLuca argues with Meredith in the hospital corridors

An image of Andrew DeLuca leaning against a wall in Grey's Anatomy

DeLuca in the hospital on Grey's Anatomy

DeLuca argues with Meredith in the hospital corridors

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Andrew DeLuca (Giacomo Gianniotti) became one of Meredith’s love interests, and he was in a constant battle with his mental health, showing signs of mania just like his father. His mental health deteriorated in season 16, to the point where Miranda Bailey (Chandra Wilson) didn’t believe him when he told her about a patient who was the victim of human trafficking. DeLuca decided to investigate the case all by himself, and while doing so, he was stabbed by an unknown assailant.

Although he seemed to be on the way to recovery, he suffered a cardiac tamponade and went into DIC, and he eventually passed away. He also convened with Meredith on the beach during her coma in Grey's Anatomy season 17, thanking Meredith for being a constant source of inspiration for him. Gianiotti's exit from Grey's Anatomy was planned from the beginning, as showrunner Krista Vernoff stated (via Looper).

"I think that he went out fighting for what he believed in. And he was through his mental health crisis. He'd become a very productive member of the hospital staff. And he wasn't going to let this woman walk away again."

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