Background. It has been suggested that cytomegalovirus infection increases the risk of ischemic heart disease. Both cytomegalovirus and ischemic heart disease are common after renal transplantation, suggesting a possible causal association in this population. Methods and Patients. We studied 1004 consecutive renal transplants with no prior history of ischemic heart disease and grafts that functioned at least 12 months. We performed univariate and multivariate analyses to examine the effect of cytomegalovirus disease and other risk factors (measured during the first posttransplant year) on the development of primary ischemic heart disease events after the first posttransplant year. Results. More than 1 year after transplantation, 116 patients (11.6%) experienced their first ischemic event (75 myocardial infarction, 12 percutaneous angioplasty, 18 bypass grafting, and 11 deaths). Patients with ischemic heart disease were more likely to have known risk factors (age, diabetes, smoking, hypercholesterolemia, systolic blood pressure, low serum albumin, and acute rejections). However, the incidence of cytomegalovirus disease was not different for those with or without ischemic heart disease (36.2% vs. 31.1%). Moreover, a similar proportion of those with and without ischemic heart disease (19.8% vs. 15.5%) had a rise in cytomegalovirus antibodies during follow-up. By multivariate analysis, risk factors for ischemic heart disease (P<0.05) were age, diabetes, smoking, low serum albumin, and two or more acute rejections during the first year. Cytomegalovirus disease was not associated with ischemic heart disease events: unadjusted relative risk=1.14 (95% confidence interval 0.78-1.67, P=0.485). After adjusting for multiple risk factors, the relative risk was 0.91 (0.60-1.37, P=0.657). Conclusion. These data suggest that cytomegalovirus disease is not a significant risk factor for the development of primary ischemic heart disease after renal transplantation.