Key PointsQuestionAre antibiotics and antibiotic exposure timeframes associated with acute graft-vs-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT)?FindingsIn this cohort study including 2023 patients and using 3 orthogonal approaches applied to antibiotic use between 7 days before and 30 days after allo-HCT procedures, several antibiotics and exposure timeframes were found to be associated with aGVHD rates. Most notably, carbapenems and penicillins with a β-lactamase inhibitor used during the first 2 weeks after allo-HCT were consistently associated with increased hazard of aGVHD.MeaningThese findings suggest that aGVHD risk should be considered in antibiotic stewardship programs during allo-HCT.