AbstractObjectivesAntibiotic use varies widely between hospitals, but the influence of antimicrobial stewardship programs (ASPs) on this variability is not known. We aimed to determine the key structural and strategic aspects of ASPs associated with differences in risk-adjusted antibiotic utilization across facilities.DesignObservational study of acute-care hospitals in Ontario, CanadaMethodsA survey was sent to hospitals asking about both structural (8 elements) and strategic (32 elements) components of their ASP. Antibiotic use from hospital purchasing data was acquired for January 1 to December 31, 2014. Crude and adjusted defined daily doses per 1,000 patient days, accounting for hospital and aggregate patient characteristics, were calculated across facilities. Rate ratios (RR) of defined daily doses per 1,000 patient days were compared for hospitals with and without each antimicrobial stewardship element of interest.ResultsOf 127 eligible hospitals, 73 (57%) participated in the study. There was a 7-fold range in antibiotic use across these facilities (min, 253 defined daily doses per 1,000 patient days; max, 1,872 defined daily doses per 1,000 patient days). The presence of designated funding or resources for the ASP (RRadjusted, 0·87; 95% CI, 0·75–0·99), prospective audit and feedback (RRadjusted, 0·80; 95% CI, 0·67–0·96), and intravenous-to-oral conversion policies (RRadjusted, 0·79; 95% CI, 0·64–0·99) were associated with lower risk-adjusted antibiotic use.ConclusionsWide variability in antibiotic use across hospitals may be partially explained by both structural and strategic ASP elements. The presence of funding and resources, prospective audit and feedback, and intravenous-to-oral conversion should be considered priority elements of a robust ASP.