The attack took place around midnight in Qutab Khel village, five kilometres (three miles) south of Miranshah, the main town of North Waziristan tribal region, a stronghold for Taliban and Al-Qaeda linked militants.
"A US drone fired two missiles on a militant compound, killing at least three suspected insurgents," a senior security official told AFP.
A security official in Peshawar confirmed the attack and casualties.
Another official in Miranshah put the death toll at four and said a fifth militant was seriously injured.
The identities of those killed in the strike were not immediately known but officials suspect that they were of Afghan origin.
North Waziristan is one of Pakistan's seven semi-autonomous tribal regions which Washington considers to be a major hub of Taliban and Al-Qaeda militants plotting attacks on the West and in Afghanistan.
Pakistani government criticises drone strikes as a violation of sovereignty and counterproductive to anti-terror efforts. But ties with Washington have nevertheless improved this year after lurching from crisis to crisis in 2011 and 2012.
Last month a US drone attack on a seminary linked to the feared Haqqani militant network in Khyber Pakhtunkhwa province in the northwest killed at least six people.
The attack, which militant sources said killed the Haqqanis' spiritual leader along with five others, was extremely unusual as it was mounted outside Pakistan's lawless tribal areas on the Afghan border.
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