The drones struck before dawn, firing four missiles at the compound and a vehicle in Mir Ali, 25 km from Miranshah, the main town of North Waziristan Agency.
US and Afghan officials have described the area as a hub for Al Qaeda and Taliban elements.
Twelve militants were killed instantly while three others died later in hospital, local tribesmen said on phone from Miranshah. Reports said several persons were injured and that some foreign fighters were among the dead.
Local residents said the strike created panic among people. Tribesmen went to the site and took the injured to a local hospital.
This was the eighth drone strike in Pakistan since a crucial NATO Summit on Afghanistan ended in Chicago on May 21.
The US stepped up drone strikes shortly after the summit, where Pakistan did not make any announcement about ending a six-month blockade of supply routes to Afghanistan.
The supply lines were shut after a cross-border NATO air strike killed 24 Pakistani soldiers in November last year.
Most of the drone strikes were carried out in North Waziristan Agency, though attacks over the past two days had focussed on South Waziristan, where the Pakistan Army conducted an operation to flush out the Taliban three years ago.
Ten militants were killed when a drone hit a house in South Waziristan on Sunday. The US has intensified its drone campaign despite protests by the Pakistan government and the people.
Pakistan says the US drone strikes on its soil are a serious violation of its sovereignty and a contravention of international law, but the US insists that the spy planes are an effective way to fight militants.
The drone strikes have added to tensions between the US and Pakistan.Over 130 people have been killed in drone strikes this year.