Zach Braff is to depart Sacred Heart hospital after eight seasons on SCRUBS.
The medical comedy is about to begin its eighth instalment on US network ABC, having spent seven years on rival network NBC.
However, the next series will be Braff's last, as he moves on to further his film career.
Set in the Sacred Heart teaching hospital, the Bill Lawrence-created show tells of the lives and work of a number of doctors and nurses, typically held together by the voiceover of Braff's character Doctor John 'JD' Dorian.
Speaking on the Television Critics' Association press tour on Wednesday, Braff and Lawrence confirmed the former's departure.
When asked if he would consider returning as a guest star, the Garden State star replied: "I'd love to come back, and maybe direct some... and help with craft services if they need that!"
Lawrence commented: "The end of the show will be about JD leaving the hospital.
"When you leave, it's about holding on to your relationships."
However, he added: "You can't kill this show."
ABC spokesman Stephen McPherson denied that the eighth season was to be Scrubs' last, saying: "We do think there's an opportunity after that."
He added: "There's a great opportunity for growth there," mooting the possibility of the show becoming a comedic version of ER, with a crop of new doctors joining the cast.
"Hopefully it will not be a one season situation [on ABC]."