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BACKGROUND: Prophylaxis against infection after a hematopoietic stem-cell transplant (HSCT) is a standard of care requiring a variety of anti-infective agents. In November 2017, letermovir was approved for cytomegalovirus (CMV) infection or disease prophylaxis in CMV-seropositive adults who had undergone an allogeneic HSCT. In January 2018, letermovir was added to the Karmanos Cancer Center’s Detroit, MI, formulary, to be used in high-risk allogeneic HSCT recipients, starting on day 10 post-transplant through day 100 post-transplant. OBJECTIVE: To evaluate the rates of CMV infection at week 24 before and after the implementation of CMV prophylaxis with letermovir in high-risk HSCT recipients who are CMV-seropositive or CMVseronegative with a CMV-seropositive stem-cell donor. METHODS: We conducted a retrospective chart review at Karmanos Cancer Center to assess the efficacy of letermovir for CMV prophylaxis in allogeneic HSCT recipients. The study eligibility criteria included age ≥18 years, post–allogeneic HSCT status, and CMV-seropositive recipient or CMVseronegative recipient with a CMV-seropositive donor. The patients were divided into 2 cohorts: a historical control group and a letermovir-recipient group. The historical control group included patients who had undergone an allogeneic HSCT between March 1, 2017, and February 28, 2018, and therefore did not receive CMV prophylaxis with letermovir. The letermovir group included patients who had an allogeneic HSCT after the approval of letermovir and received CMV prophylaxis with letermovir postHSCT between March 1, 2018, and February 28, 2019, based on the institutional standard of care. RESULTS: The final analysis included 128 patients, with 67 patients in the control group and 61 patients in the letermovir group. In the control group, 36 (54%) patients had a CMV infection compared with 6 (10%) patients in the letermovir group (P <.001). Of the patients who had CMV infection, 4 patients in the control group had documented CMV disease compared with none of the patients in the letermovir group (P = .046). The time to undetectable CMV by polymerase chain reaction (PCR) test was significantly shorter in the letermovir group than in the control group (16 days vs 29 days, respectively; P = .016). CONCLUSION: These results show that CMV prophylaxis with letermovir was effective in preventing and delaying CMV infection and resulted in a quicker clearance of CMV per serum PCR in post– allogeneic HSCT recipients who were CMV-seropositive or received stem cells from a CMVseropositive donor. [ABSTRACT FROM AUTHOR]