Burke made his final appearance in the third season, leaving Seattle in the aftermath of his failed wedding. On June 7, 2007, ABC announced it had decided not to renew Washington's contract, and that he would be dropped from the show after an on-set incident with fellow cast members T.R. Knight and Patrick Dempsey.
Preston Burke is the former chief cardiothoracic surgeon at Seattle Grace Hospital. He completed his pre-medical studies at Tulane University where he pledged Kappa Alpha Psi, and went on to graduate first in his class from Johns Hopkins Medical School. While in college, he met Erica Hahn, who graduated in second place after him, beginning a rivalry between then. He was once the interim chief of surgery while Richard Webber was healing from his brain surgery. He began a relationship with intern Cristina Yang but broke it off because he feared it would ruin both of their reputations. Her miscarriage brought them back together. He and Cristina lived together in his perfectly-kept apartment.
Towards the end of the second season, he was shot, which affected his control of his right-hand. His temporary fix to this possibly long-term problem was to work together with Cristina during every one of his surgeries so that she could take over in case he might have trouble with his hand. The arrangement fell apart after Cristina, reacting to growing stress after George O'Malley caught onto their secret, went to the Chief and confessed everything. Initially, he was engaged in a cold war with Cristina, where neither of them spoke. However, after she broke the silence, he proposed to her and she accepted his proposal. Before their secret was revealed, Burke was to become the next Chief of Surgery, but he had to compete with his fellow attending for the position. He has since recovered from the injury, after Dr. Derek Shepherd operated on him. For the remainder of the season, Preston and Cristina prepared for the wedding and experienced normal stresses that result from such a process, such as meeting each other's parents.
However, in the finale of season three, on the day of their wedding, Burke told Cristina that he no longer wished to make her do anything against her will, and realised he was trying to make Cristina the woman he wanted her to be, and not accept her as the woman she is. Cristina said she "thought this was what she wanted." He wanted her to say she knew it was what she wanted, so he left her in the chapel. Cristina then returned to their apartment and discovered Burke had left, taking with him the things that meant something to only him (his trumpet, his Eugene Foote collection, his grandmother's picture, and his lucky scrub cap), leaving Cristina devastated.
In the fourth season, Preston's long-time rival and love-to-hate medic Dr. Erica Hahn replaced him at the head of cardiothoracic surgery. Before taking over the position she had tremendous respect for Burke although she would have never admitted it to his face. Hahn disliked Cristina because of her relationships with Burke and Colin Marlow. During his employment at a new hospital, he is made the recipient of 2008's Harper Avery, a highly prestigious medical award. Cristina is later hurt that he did not mention her in his article, even though Cristina helped Burke with his recovery from an injury.
Although Burke initially disliked George, he began to like him and later, George became his guy. George even moved in with him for a while but was kicked out when Cristina walked around naked. Burke was friendly towards Derek for a while but he wasn't friends with him. He even befriended Addison Shepherd first. After a bomb scare at the hospital they became good friends. He even chose Derek to be his best man. He was good friends with Richard Webber as well.
At the mixer before the interns' first day, Cristina approached Burke but he ignored her because he was too interested in his date.
He began a relationship with intern Cristina Yang in season 1 but broke it off because he feared it would ruin both of their reputations. However, her miscarriage brought them back together. They lived together in his perfectly-kept apartment. However, after being shot he started to have tremors and they were forced to keep them secret putting a strain on their relationship. After a long time of keeping his tremors a secret, Cristina went to the Chief and confessed everything. Initially, he was engaged in a cold war with Cristina, where neither of them spoke but after she spoke to him first, he decided to propose her and she accepted.
In season 4, after leaving her at the chapel, Preston asks Derek to inform Cristina that he has handed his resignation in and told his mother to go and collect his things.
Dr. Preston Burke used to be the chief cardiothoracic surgeon at Seattle Grace Hospital on a salary of $2 million. After completing pre-medical studies at Tulane University, Burke graduated first in his class from Johns Hopkins Medical School. He was once the interim Chief of Surgery while Dr. Webber was healing from his surgery.
In the second season finale he was shot, affecting his control of his right hand.
In season four of Grey's Anatomy, Preston's long-time rival medic Dr. Hahn replaced him as the head of cardiothoracic surgery. Having such, she has some respect for Burke was infuriated when he won a medical award instead of her.
- On June 7, 2006, it was announced that Isaiah Washington was released from his contract. This was reportedly due to the controversy of Washington using the derogatory word "faggot" towards cast mate T.R. Knight during an off camera argument and following a physical altercation with Patrick Dempsey.
- Cristina rarely calls Burke by his first name, Preston.
- He plays the trumpet and enjoys jazz music, especially Eugene Foote's. He performs surgery to remove his pacemaker on his musical here at Foote's request, but against Burke's better judgement, unfortunately, Foote dies during surgery.
- Burke was the only cardiothoracic transplant specialist at Seattle Grace, a role presumably taken over by Dr. Hahn upon on his departure.
- When casting for Burke, he was described as a nebbishy, stout forty-something man.