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Objectives:  Prior studies have shown that cytomegalovirus(CMV) infection is a risk factor for the development of cardiac allograft vasculopathy(CAV) and is associated with reduced long-term survival after heart transplantation. The aim of this ISHLT Transplant Registry study was to compare post-transplant survival in different CMV donor:recipient serologic combinations. Methods:  We performed a retrospective cohort study, using the ISHLT Thoracic Transplant Registry, on 15,885 adult primary heart transplant recipients with known CMV serologic status between 7/2004 and 6/2014. Post-transplant survival and risk of developing CAV were compared across 4 groups: CMV-seronegative recipients(R-) receiving CMV-positive grafts(D+), intermediate-risk patients(D+R+ and D-R+), and low-risk patients(D-R-). Results:  Baseline characteristics (donor/recipient age, BMI, recipient serum creatinine, blood group, donor cause of death, recipient diagnosis and ischemic time) were mostly balanced between the groups. Kaplan Meier survival analyses over a follow up of 10 years revealed significantly worse survival for both D+ groups as compared to the CMV low risk group (D+R+:56.61% (95%CI 53.94,59.41) vs. D-R-:63.09% (59.74,66.64) p<.01 and D+R-:57.69% (56.03,59.39) vs. D-R-; p<.001), whereas recipient seropositivity alone was not associated with reduced survival (D-R+ vs. D-R- p=.178). The risk of developing CAV after HTx was not significantly increased in D+ as compared to D- groups. Conclusion:  In a large contemporary cohort, CMV status at the time of heart transplantation was not associated with CAV development. However, there was a significant association between donor CMV seropositivity and reduced short- and long-term survival after heart transplantation. Approaches to mitigate the impact of CMV on post-transplant survival are needed. Supplemental Visual Abstract; https://links.lww.com/TP/C292