Death with a functioning graft (DWF) is now the most common cause of late renal transplant failure, with cardiovascular disease its most frequent etiology. In some populations, infection with cytomegalovirus (CMV) increases risk of coronary disease. Few data exist regarding CMV and cardiovascular mortality after renal transplantation. We reviewed charts of 158 adult patients who died more than 90 days after receiving renal allografts and a matched cohort of 143 (of 2398) surviving patients transplanted at the University of Alabama at Birmingham between 1990 and 1998. Only advancing donor and recipient age increased risk of DWF; CMV infection did not. However, of 50 patients who died of cardiovascular causes, 94% were seropositive for CMV, while only 74% of the other 108 deaths occurred in CMV-seropositive patients (p < 0.05). Risk of cardiovascular death was greatest (p < 0.05) in patients with diabetes, advancing age, and CMV seropositivity. In renal transplant recipients, infection with CMV increases risk of death as a result of cardiovascular causes.