Grey's Anatomy

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

Grey’s Anatomy has said goodbye to many main characters, and some of them were, unfortunately, killed – here’s every one of them.

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 many years through Grey’s Anatomy’s 20 season 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.

10Denny Duquette Died After A Heart Transplant

Season 2, Episode 27 – “Losing My Religion”

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. 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.

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9Meredith’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.

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 Anatomy but 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.

8George 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

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.

7Reed 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

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.

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