ABC said Wednesday that Heigl's final appearance in the medical drama aired Jan. 21, four months before the show's season finale in May. Her departure was first reported online by Entertainment Weekly.
ABC Studios said Heigl was ending her run as Dr. Izzie Stevens by "mutual agreement."
Heigl told Entertainment Weekly that she asked to be let out of her contract 18 months early because of her new role as mother to an adopted daughter. The 31-year-old actress is married to singer-songwriter Josh Kelley.
Heigl launched a successful movie career during her tenure on "Grey's Anatomy," including the box-office hit "Knocked Up."
