*Purpose: It is unknown if donor or recipient (D/R) CMV serostatus, in the era of CMV prophylactic and pre-emptive strategies, remains associated with clinical outcomes in liver transplant (LTx) recipients. We assessed the associations between D/R CMV serostatus on graft loss and mortality in LTx recipients.

*Methods: We analyzed all adult U.S. recipients undergoing LTx from 1/1/2010 to 3/14/2020 in the OPTN database. We used univariable and multivariable mixed Cox proportional hazards regression to analyze the associations between D/R CMV serostatus and graft loss or mortality.

*Results: Patients were grouped by CMV pairings: D-/R- (n = 7,251), D-/R+ (n = 12,194), D+/R- (n = 11,903), and D+/R+ (n = 22,730). During a mean follow-up of 3.3 ± 2.7 years after LTx, 8,712 (16.1%) of recipients died and 9,703 (17.9%) had graft loss. Recipient survival at 8 years after transplant was 70.1% for D+/R-, 69.8% for D+/R+, 73.5% for D-/R+, and 73.8% for D-/R-. On multivariable regression, compared to D-/R- recipients, D+/R- recipients had significantly higher risks of mortality (adjusted HR 1.13, 95% CI 1.04 – 1.22) and graft loss (adjusted HR 1.11, 95% CI 1.04-1.2). There were no significant associations between CMV D+/R+ and D-/R+ serostatus and mortality or graft loss on multivariable analysis.

*Conclusions: Even in the era of CMV prophylactic and pre-emptive strategies, CMV D+/R- serostatus remains independently associated with decreased survival and graft loss in LTx recipients. Studies are needed to define the mechanisms underlying this association.

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