Objectives The study was conducted to determine the long-term outcome of patients who underwent heart transplantation 15 to 20 years ago, in the cyclosporine era, and identify risk factors for death. Methods A retrospective analysis was done of 148 patients who had undergone heart transplantation between 1985 and 1991 at a single center. Operative technique and immunosuppressive treatment were comparable in all patients. Results Actuarial survival rates were 75% (n = 111), 58% (n = 86), and 42% (n = 62) at 5, 10, and 15 years, respectively. The mean follow-up period was 12.1 ± 5.6 years for patients who survived more than 3 months after transplantation (n = 131). The major causes of death were malignancy (35.8%) and cardiac allograft vasculopathy (24.7%). No death related to acute rejection was reported after the first month of transplantation. Graft coronary artery disease was detected on angiography in 66 (50.3%), and 7 (5.3%) had retransplantation. Malignancies developed in 131 patients (48.1%), including skin cancers in 31 (23.6%), solid tumors in 26 (19.8%), and hematologic malignancies in 14 (10.6%). Severe renal function requiring dialysis or renal transplantation developed in 27 patients (20.6%). By multivariable analysis, the only pre-transplant risk factor found to affect long-term survival was a history of cigarette use ( p < 0.0004). Conclusions Long-term survival at 15 years after cardiac transplantation remains excellent in the cyclosporine era. Controlling acute allograft rejection can be achieved but seems to carry a high rate of cancers and renal dysfunction. History of cigarette use affects significantly long-term survival in our study.