The US space agency is targeting February 13 for the lift-off of Crew-12's mission aboard a SpaceX Falcon 9 rocket, with a window opening at 5:15am local time (1015 GMT).
The pre-dawn launch was delayed by two days over adverse weather forecasts across the US East Coast, including high winds that could have complicated any potential emergency maneuvers.
If Friday morning's launch goes as planned, the astronauts should arrive at the orbiting ISS by approximately 3:15 pm on Saturday.
Crew-12 is composed of Americans Jessica Meir and Jack Hathaway, along with French astronaut Sophie Adenot and Russian cosmonaut Andrey Fedyaev.
They have been in quarantine at NASA's Kennedy Space Center in Florida as they await blast-off.
The travelers will replace Crew-11, which returned to Earth in January a month earlier than planned in the first medical evacuation in the space station's history.
The ISS, a scientific laboratory orbiting 250 miles (400 kilometers) above Earth, has since been staffed by a skeleton crew of three.
NASA declined to disclose any details about the health issue that cut the mission short.
Once the astronauts finally arrive, they will be one of the last crews to live aboard the football field-sized space station.
Continuously inhabited for the last quarter century, the ageing ISS is scheduled to be pushed into Earth's orbit before crashing into an isolated spot in the Pacific Ocean in 2030.
- Microgravity and the human body -
The ISS, once a symbol of warming post-Cold War relations, has been a rare area of continued cooperation between the West and Russia since Moscow invaded Ukraine in 2022.
However, the space station has not entirely avoided the tensions back on Earth.
In November, Russian cosmonaut Oleg Artemyev -- who had long been planned to be a member of Crew-12 -- was suddenly taken off the mission.
Reports from independent media in Russia suggested he had been photographing and sending classified information with his phone. Russian space agency Roscosmos merely said he had been transferred to a different job.
His replacement Fedyaev has already spent some time on the ISS as part of Crew-6 in 2023.
During their eight months on the outpost, the four astronauts will conduct many experiments, including research into the effects of microgravity on their bodies.
Meir, who previously worked as a marine biologist studying animals in extreme environments, will serve as the crew's commander.
Adenot will become the second French woman to fly to space, following in the footsteps of Claudie Haignere, who spent time on the Mir space station.
When Adenot saw Haignere's mission blast off, she was 14 years old.
"It was a revelation," the helicopter pilot said during a recent briefing.
"At that moment, I told myself: one day, that will be me."
Among other research, the European Space Agency astronaut will test a system that uses artificial intelligence and augmented reality to allow astronauts to carry out their own medical ultrasounds.
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