Wyle, who plays Dr. John Carter, told E! Entertainment Television on Thursday that he plans to leave the show at the end of this season.
"I've just got other stuff going in my life right now," Wyle told "E! News Live." "I've got a son, I've got family and friends that said goodbye to me 12 years ago and are wondering when I'm coming back, and this little urge to scratch a different kind of itch in my career, and it's just coming to the end of the character's run."
Wyle was the impressionable young resident among a powerhouse cast that included Anthony Edwards, George Clooney, Eriq La Salle and Julianna Margulies. As they all left around him, Wyle became the show's promotional centerpiece.
He may have talked to E! about leaving, but he hasn't told series creator John Wells or the producers, Warner Bros. Television, said Wyle's spokesman, Eddie George.
"He's clear on what he said," George said. "That's where his head is at. That could change. There's a lot of things that could happen between now and the end of the season."
A Warner Bros. spokeswoman said only, "people are going to have to stay tuned to see what's happening."
The five-time Emmy Award nominee's contract expires at the end of this season. This spring he watched as another popular Warner Bros. show that debuted the same season,
"The day the cast filmed their, I saw them in the commissary. It was heavy," he told The Associated Press. "Here they were, closing a defining chapter in each of their lives, and all I could do was think: 'The end of that chapter's coming, for me.'"
Earlier in the year he said he thought about leaving several times.
What made him stay?
"The money, probably," he said.
"ER" will outlast him. NBC has locked up the show for another season past this one and, barring an unexpected downturn in the ratings, it will likely continue beyond that.
"It feels like the show is on the edge of reinventing itself," Wyle told E!. "It's time to take it to that next evolutionary place, where names like George and Tony, Eriq, Julianna and Noah are a thing of the past, and names like Shane (West), Linda (Cardellini) and Parminder (Nagra) are a thing of the future."
By David Bauder
By David Bauder