The shuttle landed at the Kennedy Space Center in Florida at 11:15 a.m. EDT (15:15 GMT).
The STS-124 shuttle crew spent 14 days in orbit installing the Japanese Pressurized Module to the space station. The module, which is the heaviest payload delivered to the world's sole orbiter, is the second unit of the massive Kibo laboratory complex. The first unit, an experimental logistics module, was delivered to the ISS in March.
The crew was commanded by Mark Kelly, 44, with Ken Ham serving as pilot. Mission specialists included Karen Nyberg, Ronald Garan, Michael Fossum and Japanese Aerospace Exploration Agency (JAXA) astronaut Akihiko Hoshide. Garrett Reisman, who had been on the ISS for three months, also returned to Earth onboard Discovery, NASA said.