Background: Managing immunosuppression is a significant aspect of posttransplantation patient care. Previously, our institution reported that prednisone could be withdrawn in cardiac allograft recipients without jeopardizing midterm survival. We returned to this group of patients to investigate the long-term effects of our steroid taper protocol. Methods: We reviewed the records of 162 consecutive cardiac transplant recipients from our institution. Patients who underwent transplantation between 1988 and 1990 were treated with traditional triple-therapy immunosuppression (cyclosporine, azathioprine, and prednisone). Beginning June 1990, we instituted a protocol of early steroid taper with discontinuation by 6 months after transplant. The two groups were comparable with respect to age, sex, ethnicity, cause of heart failure, ischemic time, body mass index, and creatinine at the time of transplantation. Results: Fifty-seven percent of the patients in the early steroid taper group were successfully withdrawn from steroids at 6 months after transplantation. This group had a decreased freedom from and increased frequency of acute rejection (p < 0.01 for each) when compared with the traditional therapy group. There was, however, no difference in freedom from posttransplant coronary artery disease (p = 0.53). The early steroid taper group enjoyed an increased freedom from malignancy (p = 0.01) and trended toward a decreased frequency of infection (p = 0.10) and improved survival (p = 0.06). Conclusions: Steroid withdrawal is possible in 57% of patients at 6 months after transplantation. The institution of an early steroid taper protocol improves the overall freedom from malignancies and may decrease the frequency of infection and prolong overall survival without increasing the risk of posttransplant coronary artery disease.