He was selected as an astronaut in 1996, and assigned to the Spacecraft Systems/Operations Branch of NASA's Astronaut Office. In July 2001 he flew his first mission aboard Atlantis, to install a new airlock module on the International Space Station (ISS). His flight in 2003 was postponed due to the Columbia tragedy that year. He returned to space in August 2007 as pilot of space shuttle Endeavour to the ISS, then again in November 2009, when he was commander of the 31st shuttle flight to the ISS. Hobaugh resigned from NASA in August 2011, after logging more than 876 hours in space.