Background: Previous studies of allograft rejection have focused on early episodes and risk factors from pretransplant variables. Methods: This multiinstitutional study compared early (<1 year) and late (> 1 year) rejection episodes and risk factors for recurrent rejection from variables both before and after transplantation among 1251 patients who underwent primary heart transplantation and available follow-up of greater than 1 year. Results: There were a total of 1882 rejection episodes over a mean follow-up of 26 ± 0.3 months. The hazard function (instantaneous risk per patient per month) peaked at 1 month followed by a low constant risk of rejection after 12 months. By multivariable analysis, the most dominant risk factors for recurrent rejection during the first posttransplantation year were a shorter time interval since transplantation and a shorter time since a previous rejection episode. Other factors included young age, female gender, female donor, positive cytomegalovirus serology, prior infections, and OKT3 induction. In contrast, after the first year, the dominant risk factors for rejection were a greater number of rejections during the first year and the presence of prior cytomegalovirus infections. Conclusions: These data show a striking time dependency for rejection episodes among heart transplant recipients. Factors that increase risk for rejection in the first year differ from risk factors for rejection in subsequent years. These data suggest that it may be possible to tailor rejection surveillance protocols and immunosuppression intensity, according to specific patient and time-related risk factors.