"I think we all anticipated that there would be glitches," Obama said. "I don't think I anticipated or anybody anticipated the degree of the problems with the website."
The president celebrated the fact that three million Americans have signed up for Obamacare since its implementation last fall.
O'Reilly repeatedly asked Obama why Kathleen Sebelius, the secretary of Health and Human Services, hasn't been fired since the enrollment website faced such a tumultuous rollout.
"My main priority right now is making it sure it delivers for the American people," Obama said. "I promise you we've held everybody up and down the line accountable."
The Fox News host then asked whether repeatedly telling Americans that, if they liked their health care plan, they could keep it under the new health care law, was "the biggest mistake of his presidency."
"This is one I regret and I've said I regretted," said Obama.
Obama participates in an interview with the network airing the Super Bowl every year. In the past, he’s sat down with Katie Couric, Matt Lauer and Scott Pelley.