The 61-year-old swimmer had reached roughly the halfway point of her journey.
Veteran swimmer Diana Nyad had been attempting a 103-mile-long swim from Cuba to Florida.
The 61-year-old had to abort the attempt early Tuesday morning after 29 hours of swimming.
Reports said she had encountered strong winds and had been vomiting when she was finally pulled from the water.
Marathon swimmer Diana Nyad announced early Tuesday that she was forced to end her second attempt to swim from Cuba to the Florida Keys.
"It's over," said a short message sent over Nyad's Twitter feed to the thousands of people following the 61-year-old's record attempt.
After reaching just short of the halfway point of her some 103-mile swim, Nyad encountered a "combination of factors" that proved to be too much to safely continue, according to an explanation posted on Twitter. She was about 29 hours into the swim. Twitter CNN, which had been tracking Nyad's swim via GPS, reported she was vomiting when she was pulled out of the water at about 12:45 a.m. The network said ocean swells, shoulder pain and asthma forced her to quit.
"I am not sad. It was absolutely the right call," CNN quoted her as saying.
Winds of 5 to 10 knots had blown Nyad off course to the east and the veteran swimmer decided to call off the attempt, herself, according to the Twitter feed. She had hoped to climb out of the water at the Southernmost Point in Key West, Fla.
Early this morning Nyad was on board her support boat, wrapped in blankets, according to the Twitter feed.
Her first attempt at the swim was more than 30 years ago and she made it about 76 miles before conditions forced her out of the water. In that attempt Nyad quit after 41 hours and 49 minutes due to strong currents and rough weather that had banged her around in the shark cage she was swimming within.
In this attempt Nyad was not using a shark cage, but instead was relying on an electrical shark shield system to keep the predators at bay.
Nyad had started her swim at Havana's Hemingway Marina at about 7:45 p.m. ET on Sunday night, according to CNN. Nyad had been hoping to complete the swim in about 60 hours.
Had her latest bid been successful, Nyad would have broken her own record of 102.5 miles for a cageless, open-sea swim, set in 1979 when she swam from the Bahamas to Florida.