Background: Cytomegalovirus seropositive (CMV+) recipients of CMV seronegative (CMV-) hematopoietic cell allografts are at the highest risk for CMV reactivation. Inspired by the recently described effect of antibiotic (abx)-induced dysbiosis on anti-viral immunity, we retrospectively evaluated whether antibacterial abx exposures influence the risk of CMV reactivation after CMV- to CMV+ cord blood (CB) or matched sibling donor (MSD) transplantation, the serologic setting with highest risk of CMV reactivation. Methods: We identified 213 eligible patients (pts; 146 CB, 67 MSD, mean age 50, range 18-73). Exposures to fluoroquinolones (FQN), 3rd or higher generation cephalosporins (CPN3+), intravenous vancomycin (Vanc), piperacillin-tazobactam (Pip-Tazo), carbapenems, and metronidazole/clindamycin (Metro/Clinda) from day (D) -7 to D +14 (binary variables) or until CMV reactivation (or D +100, whichever occurred first; time-varying variables) were included in multivariable Fine-Gray regression models with competing risk for non-CMV death to estimate the risk of CMV reactivation by D +100. Other pre-defined covariates were ATG use during conditioning, anti-CMV abx exposure for other viruses, and acute GVHD. Results: 91% of pts received FQN, 67% CPN3+, 56% Vanc, 21% Pip-Tazo, 22% carbapenems, and 28% Metro/Clinda until D +14. These numbers increased to 94%, 81%, 76%, 31%, 38%, and 39% by D +100 (or CMV reactivation), respectively. 83 pts (39%: 66 CB, 17 MSD) had CMV reactivation by D +100. Vanc exposure by D +14 almost doubled the risk of CMV reactivation (HR 1.96, 95%CI 1.11-3.46, P = 0.02). With abx exposures up to D +100 modeled as time-varying covariates, Vanc exposure predicted a higher risk for CMV reactivation (HR 1.86, 95%CI 0.99-3.52, P = 0.06). The table below summarizes the results, excluding non-abx covariates for brevity. Conclusions: Our results suggest that vancomycin-sensitive bacteria may protect against CMV reactivation. Identifying the specific taxa and their location (intestinal vs. extraintestinal) requires more research. Microbiota considerations and abx exposure patterns can help personalize CMV prophylaxis.