The former costars appeared together at a special New York City screening of The Tender Bar, a new coming-of-age film from Clooney, 60, starring Ben Affleck and Tye Sheridan.
Margulies, 55, was photographed smiling with Clooney at the Wednesday screening, where she caught up with her former onscreen love interest.
The actors worked together on ER from 1994-2000, with Clooney playing Dr. Doug Ross and Margulies starring as nurse Carol Hathaway. The two played a couple on the hit medical drama, and Margulies told PEOPLE in April that she and her costar were so convincing onscreen because they had feelings for each other in real life.
Frazer Harrison/Getty Images for Turner
"That can't happen if you don't have a crush on each other," Margulies said of her and Clooney's ER chemistry. "And with George and me, it was so organic. I was just supposed to be a guest star, number 39 on the call sheet. But he treated everyone the same."
She added that Clooney acted as her "mentor" on the show, explaining, "I followed and watched how he conducted himself on the set. When you create an environment that people feel safe in, then you do your best work. And George taught me that."
Margulies continued, "I felt so safe with him. I mean, I never thought, 'Well, why would I be in the bathtub and he's coming in?' I was like, 'Okay, I'll be in the bathtub. Yeah, great.' "
Although Margulies left ER in 2000, she reunited with Clooney and the rest of her costars for a live virtual cast reunion for Stars in the House, which took place over Zoom in April. And while she told WSJ. Magazine she was "thrilled" to take part in the spring event, she's ruling out any possibility of an ER reboot.
"What kind of possible reunion can you have with people 30 years older than they were when they first started out?!" she told the magazine earlier this month. "I guess it's only going to be embarrassing as far as I'm concerned."
Similarly, Clooney was hesitant about an ER reboot when the subject came up during the April virtual reunion.
"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," the actor said. "I'm not sure that that's available."
He added, "I'm not sure [about a reboot]… it's hard to catch lightning again."