A video feed from NASA showed the capsule carrying American astronauts Mike Fincke and Zena Cardman, Russian cosmonaut Oleg Platonov and Japanese astronaut Kimiya Yui land off the coast of San Diego at 12:41 am (0841 GMT).
"On behalf of SpaceX and NASA, welcome home," mission control told the crew moments after landing.
"It's so good to be home, with deep gratitude to the teams that got us there and back," Cardman replied.
A health issue prompted their mission to be cut short, after spending five months in space.
The US space agency has declined to disclose any details about the health issue but stressed the return was not an emergency situation.
The affected crewmember "is doing fine," NASA Administrator Jared Isaacman told reporters after the splashdown.
Isaacman said only that the crewmember experienced "a serious medical condition" that "could have happened on Earth completely outside of the microgravity environment."
He said all crewmembers are safe, in good spirits and were undergoing standard post-arrival medical checks.
"They just executed... a near-perfect mission on orbit," Isaacman said.
Fincke, the SpaceX Crew-11 pilot, shared a similar message in a social media post earlier this week: "First and foremost, we are all OK. Everyone on board is stable, safe, and well cared for."
"This was a deliberate decision to allow the right medical evaluations to happen on the ground, where the full range of diagnostic capability exists. It's the right call, even if it's a bit bittersweet."
The Crew-11 quartet arrived at the ISS in early August and had been scheduled to stay onboard the space station until they were rotated out in mid-February with the arrival of the next crew.
James Polk, NASA's chief health and medical officer, previously said "lingering risk" and a "lingering question as to what that diagnosis is" led to the decision to bring back the crew earlier than originally scheduled.
- Ready for the unexpected -
The crew conducted a little under 900 hours of experiments during its 167 days in orbit, said Joel Montalbano, deputy associate administrator of NASA's Space Operations Mission Directorate.
American astronaut Chris Williams and Russian cosmonauts Sergey Kud-Sverchkov and Sergei Mikaev, who arrived at the station in November aboard a Russian Soyuz spacecraft, remained on the ISS.
The Russian Roscosmos space agency operates alongside NASA on the outpost, and the two agencies take turns transporting a citizen of the other country to and from the orbiter -- one of the few areas of bilateral cooperation that still endure between the United States and Russia.
Continuously inhabited since 2000, the International Space Station seeks to showcase multinational cooperation, bringing together Europe, Japan, the United States and Russia.
Located some 400 kilometers (248.5 miles) above Earth, the ISS functions as a testbed for research that supports deeper space exploration -- including eventual missions to return humans to the Moon and onward to Mars.
The four astronauts who were evacuated had been trained to handle unexpected medical situations, said Amit Kshatriya, a senior NASA official, praising how they have dealt with the situation.
The ISS is set to be decommissioned after 2030, with its orbit gradually lowered until it breaks up in the atmosphere over a remote part of the Pacific Ocean called Point Nemo, a spacecraft graveyard.
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