Some data suggest that cytomegalovirus (CMV) may be involved in atherogenesis. However, there are few data suggesting that CMV may contribute to posttransplantation atherosclerosis. We studied a cohort of 570 consecutive renal transplant recipients. The impact of CMV on atherosclerotic events was analyzed with respect to other known main cardiovascular risk factors. The mean follow-up duration (± SD) was 87 ± 31 months. A total of 357 patients were considered to be CMV exposed, and 213 were considered to be CMV naive. Cox regression analysis revealed that CMV exposure (hazard ratio [HR], 1.80 [95% confidence interval {CI}, 1.06-3.05]; P = .030) was an independent risk factor for atherosclerotic events. A total of 213 patients remained CMV negative during follow-up, 225 CMV-positive patients had no replication after transplantation, and 132 CMV-positive patients experienced CMV replication after transplantation. Atherosclerotic event rates were 8.5%, 13.3%, and 18.2%, respectively (P = .034). Cox regression analysis revealed that patients with posttransplantation CMV replication had an increased risk of atherosclerotic events (HR, 2.06 [95% CI, 1.03-4.15]; P = .042) and death (HR, 1.76 [95% CI, 1.08-2.89]; P = .024). There was also a trend toward an increased risk of atherosclerotic events in CMV-positive patients without posttransplantation replication (HR, 1.62 [95% CI, .91-3.05]; P = .098). Both pretransplantation CMV exposure and posttransplantation CMV replication contribute to the increased risk of cardiovascular disease in transplant recipients.