"Secondly the only people that we fire on are confirmed terrorist targets at the highest levels after a great deal of vetting."
Kerry insisted at an event hosted at the University of Addis Ababa: "I am convinced that we have one of the strictest, most accountable and fairest programmes."
Each target was carefully monitored and "sometimes it takes a year to build the authority to know that you're correct," Kerry said.
"We do not fire when we know there are children or collateral, we just don't. We have absolutely not shot at high-level targets when we have seen that there are people there," Kerry said.
The US "preference" was to capture suspects wanted by US agencies, Kerry said, maintaining that Islamic militants did not use the same caution when they attacked American or Western targets.
"I will tell you that the extremists who put bombs in those mosques never engage in the kind of clear discretion we have used in this programme," he said.
But he also maintained that America was not engaged in a war against Islam, and acknowledged that there had been mistakes by the United States.
Kerry also defended the US move to try open talks with the Taliban leadership, saying it was better to try to bring people to the table to resolve issues rather than try to fight it out.
"Years ago people thought the United States should not talk to China because of Mao Zedong," he told the event, hosted by the BBC, just hours before leaving for Amman.
"People thought we shouldn't talk to the Vietnamese during that war... but even as we fought them we had discussions in Paris about peace."