The attack took place in the early hours of Friday, when CIA-operated Predator drones circled the village of Damadola in the Bajaur area in northwest Pakistan before launching four Hellfire missiles at a mud-walled compound. Three houses were razed to the ground and 22 people died.

US officials said the raid was based on “good reporting” of Zawahiri’s presence in the village at a dinner celebrating the Muslim Eid holiday. Intelligence officials took away four bodies for identification.

The 54-year-old Egyptian doctor has been on the run for more than four years despite a $25m (£14m) price on his head and is said to have had narrow escapes in the areas between Pakistan and Afghanistan.

Damadola lies in this rugged, mountainous area, just five miles from Afghanistan. When Pakistani intelligence received a tip-off that Zawahiri was there, it seemed to be a likely hideout. The village is controlled by a pro-Taliban party, the Tehrik Nifaz Shariat-i-Mohammadi, led by the charismatic Sufi Mohammad, whose supporters are believed to help Taliban and Al-Qaeda leaders on the run.

The neighbouring Afghan province of Kunar is dominated by Gulbuddin Hekmatyar, the fundamentalist warlord with whom Zawahiri has close ties.

As the dead were buried yesterday amid angry scenes, villagers confirmed that their Eid guests had included four men who had come from Afghanistan. But they insisted that the four were not high-level Al-Qaeda officials as claimed. “We live on the border and all have friends and relatives on both sides,” said one villager.

Among the mourners was Shah Zaman, who lost two sons and a daughter in the attack. “I ran out and saw planes,” he said. “I ran towards a nearby mountain with my wife. When we were running we heard three more explosions and I saw my home being hit.”

Sahibzada Haroon Rashid, a member of parliament who lives nearby, said the planes had targeted three houses belonging to jewellery dealers. “The houses have been razed,” he said. “There is nothing left. Pieces of the missiles are scattered all around. Everything has been blackened in a 100-yard radius.”

Last night Pakistan’s foreign ministry protested to the US ambassador over what it described as the “loss of innocent civilian lives”. Shaikh Rashid Ahmed, Pakistan’s minister of information, said: “We don’t know whether Zawahiri was there or not. We are investigating.”

Another senior government official insisted that Zawahiri was not in the village. “They acted on wrong information,” he said. One Pakistani intelligence officer claimed that Zawahiri had been present but the Americans had taken too long to react and “missed him by six hours”.

Although Al-Qaeda has been overshadowed in the past two years by events in Iraq, the killing of Zawahiri would have been the biggest coup so far in the war on terrorism. Zawahiri acts as doctor and adviser to Osama Bin Laden, its leader, who suffers from low blood pressure. He is regarded as Bin Laden’s deputy, appearing alongside him in videos.

In his trademark white turban and large glasses, Zawahiri has issued the majority of statements in the name of the organisation. In one, after the July 7 attacks in London, he threatened the Queen, calling her “one of the severest enemies of Islam”.

To miss him again is an embarrassment for Washington. In March 2004 the Pakistani military — acting with CIA back-up — thought it had surrounded Zawahiri in South Waziristan, even sending DNA from one body to be tested. Pakistan’s president, Pervez Musharraf, excitedly told CNN that Al-Qaeda’s “number one or two” had been surrounded. This proved to be false.

Friday’s attack will compound local anger against Musharraf. According to intelligence sources, it was the second attempt to assassinate Zawahiri in eight days. A missile smashed into the home of a militant cleric in the Saidgi area, also close to the Afghan border, after a tip-off that Zawahiri was there. Eight members of Maulvi Noor Mohammad’s family were killed in the attack.

Additional reporting: Mohammed Shehzad, Islamabad, Dean Nelson, Delhi

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