Both men made the move from the hospital ward to the big screen - anyone remember Clooney's ER days? - and Dempsey is now the star of new rom-com Made of Honour.
So how does the actor feel about being compared to Clooney?
"It's funny, it's very flattering and I'm having a good time and enjoying the moment while it's here," he said.
Well who wouldn't? But how would he feel about women offering to have his children and constant marriage proposals?
"Well I have children now, I don't think I could handle any more women - one is enough! So I'm very happy and I'm married. I don't need any more!" he said.
Kilt comedy
Of course, being typecast as Dr Derek Shepherd could have its drawbacks, but Dempsey doesn't seem to mind.
"I'm really pleased with the success of the show and it's allowed me to do something like this," he said.
In his new film, Made of Honour, he plays a man who realises he's in love with his friend when she asks him to be her maid of honour.
He had to sport a very short kilt for the role, which he took in his stride.
He said: "It was funny when I first put the kilt on. All the local Scots were making fun of me, telling me 'It's too short, you need a longer one!' I said 'No, no, it's a comedy, it's OK.'"
Dempsey isn't finished with the white coat just yet with more Grey's Anatomy in the pipeline. So what can we expect?
"All those other relationships resolve themselves going into season 4," he said. "I think we get back more to the first two seasons, so with a sense of humour.
"The relationships change. Hopefully Derek and Meredith get it together at some point."
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