Security officials said three unmanned US aircraft fired altogether six missiles on Datta Khel village, some 35 kilometers (22 miles) east of Miranshah, the main town of North Waziristan tribal district.
Some officials said at least 20 people were killed and 10 injured in the attacks.
Datta Khel is believed to be a stronghold of Hafiz Gul Bahadur, a Taliban commander who is accused of sending fighters across the border to fight NATO troops in Afghanistan.
The northwestern tribal region near the Afghan border is thought by the US to be a hotbed of Islamist extremists. US officials see drone attacks as a vital weapon in the area, where Pakistan is reluctant to send its army.
Friday evening's attacks were the first since Islamabad and Washington reached a deal to reopen land routes into Afghanistan, after US Secretary of State Hillary Clinton apologized for the deaths of 24 Pakistani soldiers in US air strikes in November.
A similar attack in the region last Sunday killed six militants.
The drone attacks are highly unpopular in Pakistan, where they are seen as an infringement of the country's sovereignty and have raised concerns about civilian casualties.
tj/rc (AFP, dpa)