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Posttransplant lymphoproliferative disease (PTLD) is a clinically important complication after transplant. This retrospective cohort study assessed the value of an Epstein–Barr virus (EBV) viral load monitoring strategy in adult liver transplant recipients to prevent EBV-positive PTLD. Visual Abstract. EBV Monitoring Strategy Reduces PTLD Incidence After Liver Transplant.: Posttransplant lymphoproliferative disease (PTLD) is a clinically important complication after transplant. This retrospective cohort study assessed the value of an Epstein–Barr virus (EBV) viral load monitoring strategy in adult liver transplant recipients to prevent EBV-positive PTLD. Background: Primary infection with or reactivation of Epstein–Barr virus (EBV) can occur after liver transplant (LT) and can lead to posttransplant lymphoproliferative disease (PTLD). In pediatric LT, an EBV-DNA viral load (EBV VL) monitoring strategy, including the reduction of immunosuppression, has led to a lower incidence of PTLD. For adult LT recipients with less primary infection and more EBV reactivation, it is unknown whether this strategy is effective. Objective: To examine the effect of an EBV VL monitoring strategy on the incidence of PTLD after LT in adults. Design: Cohort study. Setting: Two university medical centers in the Netherlands. Patients: Adult recipients of first LT in Leiden between September 2003 and January 2017 with an EBV VL monitoring strategy formed the monitoring group (M1), recipients of first LT in Rotterdam between January 2003 and January 2017 without such a strategy formed the contemporary control group (C1), and those who had transplants in Leiden between September 1992 and September 2003 or Rotterdam between 1986 and January 2003 formed the historical control groups (M0 and C0, respectively). Measurements: Influence of EBV VL monitoring on incidence of PTLD. Results: After inverse probability of treatment weighting of the 4 groups to achieve a balance among the groups for important patient characteristics, differences within hospitals between the historical and recent era in cumulative incidences—expressed as the number of events per 1000 patients measured at 5-, 10-, and 15-year follow-up—showed fewer events in the contemporary era in both centers. This difference was considerably larger in the monitoring center, whereas the 95% CI included the null value of 0 for point estimates. Limitation: Retrospective, low statistical power, and incompletely balanced groups, and non-EBV PTLD cannot be prevented. Conclusion: Monitoring EBV VL may reduce PTLD incidence after LT in adults; larger studies are warranted. Primary Funding Source: None. [ABSTRACT FROM AUTHOR]