In a further sign of the difficult path ahead to any deal between the two geopolitical foes, Trump on Monday issued a stark warning that if the talks are unsuccessful, "Iran is going to be in great danger".
Iran had pushed back against Trump's demands in recent weeks that it directly negotiate over its nuclear program or be bombed, and it appeared to be sticking to that position on Monday, saying it agreed only to mediated talks, likely to be held in Oman.
"We're having direct talks with Iran, and they've started. It'll go on Saturday. We have a very big meeting, and we'll see what can happen," Trump told reporters in the Oval Office during a meeting with visiting Israeli Prime Minister Benjamin Netanyahu.
"And I think everybody agrees that doing a deal would be preferable."
Trump said Saturday's talks with Iran would be at a very high level without elaborating. He declined to say where the talks would take place but held out the possibility that a deal could be reached.
The US and Iran held indirect talks during former president Joe Biden's term but they made little if any progress. The last known direct negotiations between the two governments were under then-president Barack Obama, who spearheaded the 2015 international nuclear deal that Trump later abandoned.
Warnings by Trump of military action against Iran had jangled already tense nerves across the Middle East after open warfare in Gaza and Lebanon, military strikes on Yemen, a change of leadership in Syria and Israeli-Iranian exchanges of fire.
Trump has said he would prefer a deal over Iran's nuclear program to a military confrontation and on March 7 he said he had written to Supreme Leader Ayatollah Ali Khamenei to suggest talks. Iranian officials said at the time that Tehran would not be bullied into negotiations.
"Iran cannot have a nuclear weapon and if the talks aren't successful I actually think it will be a very bad day for Iran," Trump said in the Oval Office on Monday.
Direct talks would not occur without the explicit approval of Khamenei, who in February said negotiations with the US were "not smart, wise, or honourable."
