Unlike all the other cargo ships that serve the space station, the SpaceX Dragon capslue is not disposable.
There, the processing and further unloading of scientific samples and returning station hardware will continue.
In a tweet, SpaceX confirmed good splashdown of Dragon in the Pacific Ocean at 10:46 a.m. EDT, about 200 miles southwest of Long Beach, California.
Some of the materials inside the Dragon will be removed and delivered to NASA immediately.
The Dragon capsule - the only such vessel capable of returning research samples and other material to Earth - remained docked with the ISS for almost a month after delivering more than two tonnes of food, water and scientific equipment for NASA on February 23.
The Dragon has now journeyed back to Earth, splashing into the Pacific Ocean in the process.
Some of the biological studies which are underway as the ISS, and whose data the spacecraft has brought back, include research on the effect of microgravity on the stem cells.
This information will provide insight into how human cancers start and spread, which aids in the development of prevention and treatment plans.
Within 48 hours of splashdown, representatives from NASA and the Center for the Advancement of Science in Space, which manages research on the ISS, will have the time-sensitive research samples from the craft in hand for analysis, NASA officials said in a statement. SpaceX and Boeing are now working towards building spacecrafts for manned-missions, according to a space.com report.
The Robotic Refueling Mission Phase 2 tested new technologies, tools and techniques that could eventually give satellite owners resources to diagnose problems on orbit, fix failures, and keep certain spacecraft instruments performing longer in space.
Space X's Falcon 9 rocket is prepared for a launch to the International Space Station February 17, 2017 at the Kennedy Space Center, Florida on LC39A, one of the renovated Space Shuttle launch pads that SpaceX leases from NASA.