Allograft coronary artery disease (ACAD) is the major factor limiting long-term survival of cardiac transplant recipients (CTRs). Although cyclosporine based triple drug immunosuppression has not decreased the occurrence of ACAD, some preliminary data suggests that prophylactic antilymphocyte preparations may reduce the incidence of this problem. All CTRs at Henry Ford Hospital have uniformly received prophylactic Minnesota Antilymphocyte Globulin (ALG), thereby providing a unique opportunity to investigate this hypothesis. One hundred three CTRs were followed for a median duration of 34 months with annual angiograms begun one year after transplant. Patients who died without an angiogram were considered to have ACAD based on autopsy results or if their death was clinically suspicious. Ninety-two patients underwent at least one angiogram. Fourteen patients had abnormal angiograms. Nine patients were identified as having ACAD by non-angiographic criteria. Five had autopsy proven disease, 3 died suspiciously, and 1 underwent successful re-transplantation for ACAD. By Kaplan-Meier analysis, the risk of developing ACAD was 12% in 1 year, 16% in 2 years, 22% in 3 years, 26% in 4 years, and 29% in 5 years. Risk of ACAD increased with older recipient's age, higher triglyceride levels, and diabetes, but was not affected by active CMV infection, number of acute rejection episodes, and HLA mismatching. These results suggest that prophylactic ALG reduces the occurrence of ACAD.