The CIA-operated spy plane fired two missiles at the compound in the mountainous region of Shawal, 70 km from Miranshah, the main town in North Waziristan Agency.
Unnamed security officials were quoted by TV news channels as saying that militants were using the compound as a training facility.
The compound was destroyed. The exact identity of those killed could not immediately be established as journalists are barred from reporting from the tribal belt.
This was the second drone strike in North Waziristan since April 29 and reflected the Obama administration's resolve to continue with its drone campaign in the face of opposition and condemnation from the Pakistan government.
The Foreign Office had condemned the last drone attack that killed four suspected militants and a junior American diplomat was summoned for the lodging of an official protest.
The Pakistan Army has so far resisted American pressure to move its troops into North Waziristan, described by US and Afghan officials as a stronghold of al-Qaeda and Taliban elements who carry out attacks on foreign forces across the border in Afghanistan.
There has been a significant drop in drone strikes after Pakistan-US ties plunged to a low last year following the unilateral American raid that killed Osama bin Laden and the cross-border NATO air strike that killed 24 Pakistani soldiers.
Today's attack was only the second one since Pakistan's parliament adopted guidelines for resetting relations with the US in March.
The guidelines included a demand for an unconditional apology for the NATO air strike and the immediate halting of drone strikes.
Pakistan describes the drone strikes as counter-productive and a violation of its sovereignty.
During US Special Envoy Marc Grossman's visit to Islamabad last month, President Asif Ali Zardari had called for setting up a mechanism to find “mutually acceptable alternatives” to drone strikes.
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