Officials from the U.S. and Iran said the initial discussions in Vienna have been constructive.
The meeting includes leaders from Russia, China, Germany, France and Britain as they try to bring the U.S. back into the 2015 nuclear deal.
The Biden administration cautioned it may take some time.
"We know these will be tough talks. We know there will be difficult discussions ahead, but again, this is a healthy step forward," State Department spokesperson Ned Price said. " It's a healthy step forward because it allows us to move forward with what we see is as the only path to achieve what President Biden and as a candidate, candidate Biden laid out. And that is a mutual return to compliance."
Meanwhile, Iran said it wants all U.S. sanctions to be lifted before it will revive the deal.
"Then we would go for full compliance. So, we have to make it clear that this is our position, but we are quite serious," Iran's Chief Nuclear Negotiator, Abbas Araqchi, said. "I have come here to do business, but i doubt that there is the same seriousness in the other side."
Officials will stay in Vienna. Another meeting is set for Friday.