CIA-operated spy plane fired two missiles targetting a house in the Birmal area of South Waziristan Agency killing three people, security sources in the region said.
Five other persons were injured in the attack, they said. It was not immediately clear which group was targeted in the strike.
More than 30 drone strikes have been reported in Pakistan, since Navy SEALs in a bold operation killed al-Qeada chief Osama bin Laden in a Abottabad.
Pakistan opposes the drone strikes but the US has ruled out any change in the campaign.
US drones routinely carry out missile strikes in the Waziristan tribal region, which the US describes as a safe haven for Taliban and al-Qaeda elements.
Today's strike came a day after Pakistan's top political leadership rejected US accusations linking the Inter-Services Intelligence agency to terror attacks in Afghanistan by the Haqqani network.
During a meeting convened by the Prime Minister yesterday, leaders of political parties backed dialogue and peaceful methods to address unrest and militancy in the tribal belt.