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Background: Recent data have demonstrated a lower incidence of cytomegalovirus (CMV) disease utilizing preemptive CMV treatment compared to universal prophylaxis in CMV seronegative liver transplant recipients who receive allografts from CMV seropositive donors (donor‐positive [D+]recipient‐negative [R−]). However, there are little data on the feasibility and outcomes after switching transplant center protocols from universal CMV prophylaxis to preemptive treatment. Methods: All D+R− adult liver transplant recipients underwent pharmacist‐led weekly monitoring of World Health Organization standardized quantitative plasma CMV deoxyribonucleic acid (DNA) after transplant for 6 months. Valganciclovir was started when plasma CMV viral load (VL) reached 100 IU/mL. All patients who were at least 12 months post‐liver transplant were retrospectively reviewed for incidence of CMV DNAemia and CMV disease in this cohort study. Results: Among 30 CMV D+R− liver transplant recipients, 23 (77%) developed target CMV DNAemia (≥100 IU/mL) at a median of 26 (range: 10–37) days after transplant with a median peak CMV VL of 947 IU/mL. Valganciclovir was started promptly with a median lag time of 1 (range: 0–5) day. There were no differences in surgical or infectious complications and readmission rates between patients with and without CMV DNAemia. Two patients had possible CMV disease in the first 6 months. None developed CMV disease in 6–12 months posttransplant. Only two patients who developed CMV DNAemia had acute cellular rejection, and none had graft loss or death. Weekly CMV polymerase chain reaction (PCR) testing was late on only three occasions for all patients before reaching the target CMV VL (<4%). Among those who remained nonviremic, 85% of scheduled weekly CMV PCR testing was completed in the first 3 months. Conclusion: Preemptive CMV treatment in high‐risk liver transplant recipients is feasible and safe. There was a low rate of CMV disease in the first 12 months post‐liver transplant with a pharmacist‐led protocol. [ABSTRACT FROM AUTHOR]