Their SpaceX capsule parachuted into the ocean just before sunset, not far from where their chartered flight began three days earlier.
WATCH | SpaceX splash down off Florida coast
The all-amateur crew was the first to circle the world without a professional astronaut.
The billionaire who paid undisclosed millions for the trip and his three guests wanted to show that ordinary people could blast into orbit by themselves, and SpaceX founder Elon Musk took them on as the company's first rocket-riding tourists.
SpaceX's fully automated Dragon capsule reached an unusually high altitude of 363 miles (585 kilometers) after Wednesday night's liftoff. Surpassing the International Space Station by 100 miles (160 kilometers), the passengers savored views of Earth through a big bubble-shaped window added to the top of the capsule.
The four streaked back through the atmosphere early Saturday evening, the first space travelers to end their flight in the Atlantic since Apollo 9 in 1969. SpaceX's two previous crew splashdowns - carrying astronauts for NASA - were in the Gulf of Mexico.
This time, NASA was little more than an encouraging bystander, its only tie being the Kennedy Space Center launch pad once used for the Apollo moonshots and shuttle crews, but now leased by SpaceX.
The trip's sponsor, Jared Isaacman, 38, an entrepreneur and accomplished pilot, aimed to raise $200 million for St. Jude Children's Research Hospital. Donating $100 million himself, he held a lottery for one of the four seats. He also held a competition for clients of his Allentown, Pennsylvania payment-processing business, Shift4 Payments.
Joining him on the flight were Hayley Arceneaux, 29, a St. Jude physician assistant who was treated at the Memphis, Tennessee hospital nearly two decades ago for bone cancer, and contest winners Chris Sembroski, 42, a data engineer in Everett, Washington, and Sian Proctor, 51, a community college educator, scientist and artist from Tempe, Arizona.
Strangers until March, they spent six months training and preparing for potential emergencies during the flight, dubbed Inspiration4. Most everything appeared to go well, leaving them time to chat with St. Jude patients, conduct medical tests on themselves, ring the closing bell for the New York Stock Exchange, and do some drawing and ukulele playing.
Arceneaux, the youngest American in space and the first with a prosthesis, assured her patients, "I was a little girl going through cancer treatment just like a lot of you, and if I can do this, you can do this."
They also took calls from Tom Cruise, interested in his own SpaceX flight to the space station for filming, and the rock band U2s Bono.
Even their space menu wasn't typical: Cold pizza and sandwiches, but also pasta Bolognese and Mediterranean lamb.
Nearly 600 people have reached space - a scorecard that began 60 years ago and is expected to soon skyrocket as space tourism heats up.
Benji Reed, a SpaceX director, anticipates as many as six private flights a year, sandwiched between astronaut launches for NASA. Four SpaceX flights are already booked carry paying customers to the space station, accompanied by former NASA astronauts. The first is targeted for early next year with three businessmen paying $55 million apiece. Russia also plans to take up an actor and film director for filming next month and a Japanese tycoon in December.
Customers interested in quick space trips are turning to Richard Branson's Virgin Galactic and Jeff Bezos' Blue Origin. The two rode their own rockets to the fringes of space in July to spur ticket sales; their flights lasted 10 to 15 minutes.
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