The unmanned flight, which is carrying 4,300 pounds of research samples and other hardware, disembarked at 11:05 a.m. EDT from the space station's Harmony module, NASA confirmed in a statement.
The ISS was over the Indian Ocean at the time the Dragon undocked.
The Dragon spacecraft will re-enter Earth's atmosphere and then make a parachute-assisted splashdown landing off the coast of Florida later Saturday.
Returning experiments include a Japanese assessment, testing the ability to create semiconductors by growing crystals in space. The experiment is aiming to create more effective solar cells and semiconductors.
An experiment conducted by the Canadian Space Agency studying accelerated vascular aging in space is also returning.
The Dragon marked the 27th commercial resupply mission carried out by SpaceX to the ISS. The spacecraft arrived at the space station March 16, propelled by a Falcon 9 rocket from Kennedy Space Center in Florida. It has been docked since its arrival.
NASA will not broadcast the landing but will post updates through its blog. The space agency did broadcast the undocking procedure live as it unfolded.
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