Hampton has undergone surgery for a torn left rotator cuff and other damage in his shoulder that will sideline him for the 2010 season, the team said Tuesday.
The 37-year-old lefty was 7-10 with a 5.30 ERA in 112 innings over 21 starts this season, his most in a year since making 29 starts in 2004 with the Atlanta Braves.
Hampton is 148-115 lifetime with a 4.07 ERA in 2,264 career innings despite spending considerable time on the disabled list with groin, calf, back and forearm problems.
Hampton left a game on Aug. 13 at Florida after five innings because of pain in his shoulder. He went on the disabled list the next day and decided about two weeks later to have the surgery.
"It's amazing that the guy was able to pitch this year," Astros manager Cecil Cooper said in Cincinnati. "It saddens me to think he had that tear in there. I think if anybody can bounce back, it's Mike. He's done that a lot."
The Astros said surgeons at the Hospital for Special Surgery in New York repaired a full tear in the rotator cuff.
Hampton, a two-time All-Star who broke into the majors in 1993, missed all of the 2006 and 2007 seasons after operations on his elbow. He was limited by a strained left pectoral muscle to 13 starts last season with Atlanta.
Hampton can become a free agent after this season. He signed an eight-year, $121 million deal with the Colorado Rockies after the 2000 season and has gone 63-62 since then.
Houston third baseman Aaron Boone, who missed the entire 2004 season because of knee surgery, said he wouldn't be surprised to see Hampton pitch again in 2011.
"I could see him coming back, just because he's had so many injuries," said Boone, who had open heart surgery in March and returned to the Astros on Sept. 2. "To his credit, he's always fought back. He takes of himself, and he's in great shape.
"The perception is people begrudge him what he makes, and he could have gone home, but he continues to battle. He's a phenomenal athlete. He's been a very good pitcher for a long time. I wouldn't put anything past him," he said.