Pilot Gregory Johnson backed Endeavour away from the space station on Monday evening, ending 12 days of linked flight. He then guided the shuttle through a loop around the orbiting complex so the crew could take pictures of its new look.
Endeavour's astronauts built a giant handyman robot and installed the first segment of Japan's Kibo lab during their stay at the station.
"We really appreciate everything you've done for us over the last couple of weeks," station commander Peggy Whitson radioed Endeavour as the shuttle pulled away. "Thanks a bunch."
The 10 space travelers performed a record-tying five spacewalks to put together the space station robot, attach the new Japanese compartment and complete other chores.
Flight director Mike Moses thanked the astronauts and the ground crew for a job well done.
"I am immensely proud of the teams, all the teams, that got us to this point," he said.
NASA's next shuttle mission is set for late May, when Discovery will deliver the enormous Japanese lab Kibo, which means hope. Endeavour delivered a storage compartment for the lab.
But the Hubble Space Telescope mission, at the end of August, might wind up being postponed because of a slowdown in shuttle fuel-tank production.
Only now, five years after the Columbia accident, are fuel tanks and their insulating foam skin being built from scratch, said LeRoy Cain, chairman of the mission management team.
The fuel tank used to propel Endeavour into orbit on March 11 was the last one that was already in production when Columbia was destroyed, and so it was easier to make the post-accident safety changes.
These changes, most if not all of them involving foam, took time to refine. NASA also became bogged down by a recurring fuel-gauge problem that finally was resolved a few months ago.
"We're on a learning curve here," Cain said.