Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at three sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy. The secondary outcome was pancreas allograft failure. Among 471 pancreas transplant recipients, 117 (24.8%) developed csCMVi after a median 226 (IQR 154-289) days. CMV D+/R- patients had a significantly higher incidence of csCMVi (HR 4.01, 95% CI 2.10-7.64; p<0.001). In adjusted analysis, a lower absolute lymphocyte count (ALC) was associated with greater risk of csCMVi among seropositive recipients (HR 1.39 per 50% decrease, 95% CI 1.13-1.73; p=0.002) but not among D+/R- patients (HR 1.04 per 50% decrease, 95% CI 0.89-1.23; p=0.595). csCMVi, lower ALC, and acute rejection (p<0.001) were independently associated with pancreas allograft failure. In conclusion, CMV D+/R- was associated with csCMVi in pancreas recipients, while ALC was associated with csCMVi only among seropositive patients. Development of csCMVi in pancreas recipients was associated with poor pancreas allograft outcomes.Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.