Allograft coronary artery disease is a major threat to long-term survival after cardiac transplantation. It has been suggested that hyperlipidemia plays a major role in allograft coronary disease. The objective of the present study was to evaluate the effect of a lipid-lowering intervention with diet and drug therapy after cardiac transplantation. Forty-six patients who underwent transplantation between 1988 and 1991 and who were treated with the American Heart Association phase 1 diet and an HMG coenzyme A reductase inhibitor (lovastatin or simvastatin) when low-density lipoprotein cholesterol levels were higher than 3.4 mmol/L were compared with 35 untreated patients having transplantation between 1983 and 1988. Annual coronary angiograms were obtained in both groups. Cholesterol, triglyceride, and low-density lipoprotein levels were significantly lower in the treated group. Actuarial survival and event-free survival (survival free from allograft coronary artery disease) were similar in both groups. Low-density lipoprotein levels lower than 3 mmol/L at the last follow-up had a positive effect on event-free survival. The cholesterol-lowering intervention was not effective in decreasing the prevalence of allograft coronary artery disease. This study suggests that more aggressive measures to lower low-density lipoprotein levels may be necessary to significantly affect allograft disease. Clinical trials should be developed to address this hypothesis.