OBJECTIVES: The aim of this study was to determine long-term survival >10 years) after cardiac transplantation in the cyclosporine era and identify risk factors influencing long-term survival. BACKGROUND Despite the availability of newer modalities for heart failure, cardiac transplantation remains the treatment of choice for end-stage heart disease. METHODS: Between 1983 and 1988, 195 patients underwent heart transplantation at a single center for the treatment of end-stage heart disease. Multivariable logistic regression analysis of pretransplant risk factors affecting long-term survival after cardiac transplantation included various recipient and donor demographic, immunologic and peritransplant variables. RESULTS: Among the group of 195 cardiac transplant recipients, actuarial survival was 72%, 58% and 39% at 1, 5 and 10 years respectively. In the 65 patients who survived > 10 years, mean cardiac index was 2.9 1/m2 and mean ejection fraction was 58%. Transplant-related coronary artery disease (TRCAD) was detected in only 14 of the 65 patients (22%). By multivariable analysis, the only risk factor found to adversely affect long-term survival was a pretransplant diagnosis of ischemic cardiomyopathy (p = 0.04). CONCLUSIONS: Long-term survivors maintain normal hemodynamic function of their allografts with a low prevalence of TRCAD. It is possible that similar risk factors that lead to coronary artery disease in native vessels continue to operate in the post-transplant period, thereby contributing to adverse outcomes after cardiac transplantation. Aggressive preventive and therapeutic measures are essential to limit the risk factors for development of coronary atherosclerosis and enable long-term survival after cardiac transplantation.