A US drone strike killed four and injured two in the Machi Khel village in North Waziristan.
Senior security officials said the target was a vehicle but two local intelligence officials said the target was a house in the village.
Local security officials said the missiles destroyed a house and put the death toll at five.
The last drone strike on Wednesday killed six people in the Data Khel region of North Waziristan.
The strike is the latest in a series of US operations in the region which are believed to have targeted Taliban and al Qaeda plotting attacks in Europe.
The United States has massively ramped up its drone campaign in the northwest tribal region on the Afghan border, amid intelligence claims of a Mumbai-style terror plot to launch attacks on European cities.
Pakistani authorities have reported 27 drone attacks, since September 3, which have killed more than 150 people in the region. Drone strikes reached an all time high in September last month.
Meanwhile, Federal Defense Minister Chaudhry Mukhtar Ahmad cautioned the drone attacks were creating problems in Pakistan’s war against terrorism, while reiterating the resolve for maintaining the sovereignty and integrity of federation.
The attack comes in the backdrop of increased pressure from the United States on Pakistan to launch an offensive against militants in North Waziristan which the Americans consider an epicentre of al Qaeda.