Original Clinical Science-GeneralBackground. There is a paucity of data on the impact of cytomegalovirus (CMV) serostatus and CMV infection on outcomes in facial vascularized composite allotransplantation. Methods. This international, multicenter, retrospective cohort study presents data on CMV and basic transplant-related demographics, including pretransplant viral D/R serostatus, and duration of antiviral prophylaxis. CMV-related complications (viremia, disease), allograft-related complications (rejection episodes, loss), and mortality were analyzed. Results. We included 19 patients, 4 of whom received CMV high-risk transplants (D+/R−). CMV viremia was noted in 6 patients (all 4 D+/R− patients and 2 D−/R+), mostly within the first-year posttransplant, shortly after discontinuation of antiviral prophylaxis (median 2 mo). CMV disease occurred in 2 D+/R− patients. The high-risk group experienced relatively more rejection episodes per month follow-up. None of D+/R− patients suffered allograft loss due to rejection (longest follow-up: 121 mo). Conclusions. D+/R− patients were at increased risk of CMV-related complications. Although a higher number of rejections was noted in this group, none of the D+/R− patients lost their allograft or died because of CMV or rejection. Thus, CMV D+/R− face transplantation can likely be safely performed with prophylaxis, active surveillance, and prompt treatment.