In an extensive analysis of open-source documents, the Bureau of Investigative Journalism found that 2,292 people had been killed by US missiles, including as many as 775 civilians.
The strikes, which began under President George W Bush but have since accelerated during the presidency of Barack Obama, are hated in Pakistan, where families live in fear of the bright specks that appear to hover in the sky overhead.
In just a single attack on a madrassah in 2006 up to 69 children lost their lives.
Chris Woods, who led the research, said the detailed database of deaths would send shockwaves through Pakistan, where political and military leaders repeatedly denounce the strikes in public, while privately allowing the US to continue.
"This is a military campaign run by a secret service which raised problems of accountability, transparency and you have a situation where neither the Pakistanis nor Americans are clear about any agreements in place and where the reporting is difficult," he said.
"All of this means that when things go wrong there is simply no redress for the families of those who have been mistakenly killed."
The research, culled from more than 2,000 news reports, leaked documents and witness statements, show how the drones gradually moved from a rarely used tool, beginning with a single strike in 2004, to a frontline weapon of war.
Notable successes include the death of Baitullah Mehsud, head of the Pakistan Taliban, in 2009. Ilyas Kashmiri, a senior al-Qaeda figure viewed as a possible successor to Osama bin Laden, is believed to have died in a drone strike in June.
However, under President Obama the strikes have been used to target low-level foot soldiers as well as senior commanders.
Today the attacks are running at a rate of one every four days, mostly centered on North Waziristan from where members of the Haqqani network launch cross-border attacks on international forces in eastern Afghanistan.
With Pakistan so far unwilling to bow to US pressure to launch a military offensive against the bases and with Islamabad ruling out any suggestion that American troops be deployed, that leaves the CIA's drones, said Imtiaz Gul, an analyst who has written extensively on the region.
At the same time, he added, they mean a president elected on a manifesto promising to close Guantanamo Bay does not have hundreds more detainees to process.
"As long as these peoples sit in jails they remain a problem, a living liability, so there seems to be a drive to kill them," said Mr Gul.
Human rights campaigners have long argued that drones represent extra-judicial killings.
Sam Zarifi, Asia-Pacific director of Amnesty International, said: "The Obama administration must explain the legal basis for drone strikes in Pakistan to avoid the perception that it acts with impunity.
"The Pakistan government must also ensure accountability for indiscriminate killing, in violation of international law, that occurs inside Pakistan." The US refuses to acknowledge the existence of its drones program.
A spokesman for the US embassy in Islamabad declined to comment.