To determine whether cytomegalovirus (CMV) disease is an independent risk factor for graft loss and death after orthotopic liver transplantation, we performed a 3-year follow-up study of 143 consecutive liver transplant recipients and six patients who underwent retransplantation. Thirty-seven patients (25%) had had CMV disease and were alive after treatment. Fifty-two deaths and eight graft losses occurred. The cumulative incidence of graft failure at 1 and 3 years of follow-up were 40% and 63%, respectively, for patients with CMV disease, compared with 22% and 33%, respectively, for those without CMV disease (P< .05, logrank test). Cumulative probabilities of survival for patients with and without CMV disease were 64% and 82%, respectively, at 1 year and 46% and 69%, respectively, after 3 years (P< .05, logrank test). Multivariate analysis with use of a time-dependent Cox model showed that previous CMV disease was an independent risk factor for graft loss at 1 and 3 years of follow-up (P= .04 andP= .007) and for patient survival (P= .04 andP= .01). Our results indicate that CMV disease is a significant independent risk factor for graft loss and patient survival after liver transplantation.