This was the first such attack since parliament last month approved new guidelines on relations with the United States, which included a call for an end to drone strikes in Pakistani territory.
"A US drone fired two missiles on a compound, killing three militants and wounding two others," a senior security official told AFP.
He said that the compound in the market area of Miranshah was once a girls' school that was occupied by the militants.
Another security official, who confirmed the toll, said the compound was used mainly by Uzbek and Tajik militants.
Pakistan wants drone strikes to stop, arguing that they are counter-productive because they kill civilians, exacerbate anti-US sentiment and violate sovereignty.
Pakistan reiterated its opposition to these attacks to Marc Grossman, the US special representative for Afghanistan and Pakistan, who visited Islamabad on Thursday amid efforts to mend fractured relations.
The parliamentary guidelines also include a ban on transporting weapons through the country to Afghanistan and an unconditional apology for US air strikes in November that killed 24 Pakistani soldiers.