The actor became a household name after playing Dr. Doug Ross for 15 seasons on the medical drama - which ran from 1994 to 2009 - but suggested he wouldn't be up for reprising the role if the show was to return to screens because he's unconvinced it could match the consistent quality displayed in the programme's original run.
Asked about the possibility during a live virtual reunion of the "ER" cast on "Stars in the House" to support co-star Gloria Reuben's non-profit organisation, Waterkeeper Alliance, he said, "I don't know. The hardest part is that when you look at the show and consistently over so many years - it would be hard to say that you could do it at the level that we did it. I'm not sure that that's available."
George has been enjoying old episodes of the show recently with his wife Amal and praised the series as "such great television."
He gushed about the show's season one episode "Love's Labor Lost", "This is better than anything I see in film or anywhere. This is stunning. It's stunning work."
"I felt that way about a lot of episodes I watched. I'm not sure (about a reboot)… it's hard to catch lightning again."
His former co-star Julianna Margulies agreed, insisting a reboot would "cheapen" the show's legacy.
The actress - who played Carol Hathaway - said, "You can't capture lightning in a bottle twice. I think you have to leave what was so beautiful and move on, because it just feels cheap… It would cheapen it for me."
However, Ming-Na Wen admitted she'd enjoy returning to play Jing-Mei Chen just because it would mean she could reconnect with the cast again.
She said during the reunion, which was streamed on People magazine's social channels, "I would love to reboot only to be able to hang out with this group of people, the talent."
"As you get older, the appreciation level and the awareness is so much greater. Just such great fortune. I would love to have been, even now… just even this, surrounded by these people."
George admitted he'd been "excited" about reconnecting for the virtual reunion.
He said, "I'm excited to see this gang. These are people that I really love, you know, and that - we grew up together, really grew up together, in many ways, and it's fun to see you guys."