The trip was always set to be the riskiest of Biden's presidency as he tried to juggle support for Israel after the October 7 Hamas attacks with efforts to prevent a humanitarian disaster in Gaza and to avert a wider war.
But his regional balancing act came undone on the eve of his visit with news of the hospital explosion -- for which Hamas blamed Israeli strikes, while Israel said it was caused by a rocket misfired by militants in Gaza.
As Biden, 80, climbed the steps of Air Force One, Jordan announced that a planned four-way summit with Palestinian president Mahmud Abbas, Jordanian King Abdullah II and Egypt's president Abdel Fattah al-Sisi was off.
It would be held "when the decision to stop the war and put an end to these massacres has been taken," said Foreign Minister Ayman Safadi.
Biden later said he was "outraged" by the "explosion" at the hospital and had told his national security team to get more information on what had happened.
- 'Solidarity' -
White House National Security Council spokesman John Kirby however told reporters aboard the presidential plane said that the Israelis "feel very strongly this was not caused by them."
He added that it was a "mutual decision" to cancel the Jordan trip after Abbas said he wanted to return home for three days of mourning, and that Biden would speak to him and Sisi by phone on the plane home.
Yet Biden will now be flying into an even more volatile situation than before, with the hospital strike sparking anger across the region.
Furious protesters tried to storm the Israeli embassy in Amman where Biden was due to meet the other leaders, while in Tehran hundreds rallied outside the French and British embassies.
Lebanon's Iran-backed Hezbollah called for a "day of rage" over the strike to coincide with Biden's arrival, fueling fears of the very escalation by Tehran and its allies that Biden's visit is supposed to warn against.
The White House said Biden wanted to "continue to stand in solidarity with Israel" after Hamas burst through its heavily fortified Gaza border, shooting, stabbing and burning to death more than 1,400 people, most of them civilians.
Biden would hold talks with Israeli Prime Minister Benjamin and his war cabinet, as well as meeting the families of some of those killed and missing in the attacks, it said.
Kirby insisted however that Biden would ask Netanyahu "tough questions" about his plans for the war.
- 'Risks' -
The NSC spokesman added that he was "optimistic" that aid would start to get through to stricken Gaza.
The Democratic president deliberated carefully before accepting the invitation to visit from right-winger Netanyahu, who has ordered preparations for what is expected to be a bloody ground offensive against Hamas in Gaza.
There was always a risk that by coming to Israel Biden would find himself too closely associated with the Israeli bombardment of Gaza, which has leveled huge swaths and killed more than 3,000 people, and the siege of the enclave.
Even before the hospital attack, the New York Times called it a "trip fraught with risks."
Anger over the hospital strike could meanwhile undermine the wider purpose of Biden's visit as he tries to prevent the Israel-Hamas war engulfing the wider Middle East.
Biden has warned Iran and Hezbollah not to get involved and has dispatched two aircraft carriers to the eastern Mediterranean to deter them.
Kirby again said there were no plans to put US boots on the ground but added that the American military assets were in place to "demonstrate a sincere capability of protecting and defending" US national security interests.
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