Piland's most recent concussion came on Sept. 7 against Temple.
"It was not easy to hear that I can no longer play the game I love, but I know that our medical staff has my best interests in mind," Piland said.
Piland, a junior, ends his career with 5,790 yards passing and 41 touchdowns. He started 10 games last season and threw for 2,929 yards and 16 touchdowns with 12 interceptions.
His first starts for Houston came in 2010, after Case Keenum suffered a season-ending injury in the third game.
Piland set an NCAA record for attempts in a game without an interception with 77 last season against Louisiana Tech.