U.S. Secretary of State John Kerry is due to start two days of talks with senior Iranian officials on Tehran's disputed nuclear program on February 22.
On the eve of the negotiations, Kerry said "significant gaps" remained, and warned President Barack Obama was ready to walk away from the talks if Tehran fails to take the steps needed to prove its nuclear program is solely peaceful.
The discussions in Geneva, Switzerland come as the two sides try to resolve differences before a March 31 deadline for a basic framework agreement.
Iranian Foreign Minister Mohammad Javad Zarif is leading the Iranian delegation.
U.S. Energy Secretary Ernest Moniz will also attend the talks, the first time he has participated in the Iran negotiations.
Kerry said because of the nature of the nuclear talks it was deemed necessary and appropriate to have technical experts, including Moniz, present.
World powers and Iran have set an end of March deadline for a framework agreement, with four further months for the technical work to be ironed out.
Iran's negotiations with "P5+1" - the United States, Britain, France, Germany, Russia and China - have already missed a November 2014 target date.
Obama has said a further extension would make little sense without a basis for continuing discussions.
Kerry said there was no doubt Obama was serious.
The president, he said, "is fully prepared to stop these talks if he feels that they're not being met with the kind of productive decision-making necessary to prove that a program is in fact peaceful."
Commentators say if the talks fail, momentum may grow in the U.S. Congress to support passing new sanctions against Iran.
Such a move could damage any hopes of reaching a diplomatic solution to the 12-year standoff over Tehran's nuclear program.
Iran denies Western charges it is secretly developing a nuclear weapons program.
Western officials say Washington decided to send Moniz only after Iran announced that Iran nuclear chief Ali Akbar Salehi Salehi was coming.
Among issues they are expected to discuss are the number of centrifuges Iran can operate to enrich uranium, and the future of a planned heavy water reactor that could produce substantial amounts of plutonium — which like enriched uranium is a potential pathway to nuclear arms.
According to Iranian media, also taking part in the talks will be Hossein Fereydoon, the brother as well as close advisor to President Hassan Rohani.
"Fereydoon's presence is prompted by the need to engage in consultations and make necessary coordinations throughout the present round of talks in Geneva," foreign ministry official Mohammad Ali Hosseini said.
"Today Geneva is the epicenter of U.S.-Iranian diplomacy over the remaining nuclear issues," he was quoted as saying by state news agency IRNA.