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OBJECTIVES: To determine if antibiotic prescribing in community nursing homes (NHs) can be reduced by a multicomponent antibiotic stewardship intervention implemented by medical providers and nursing staff and whether implementation is more effective if performed by a NH chain or a medical provider group. DESIGN: Two‐year quality improvement pragmatic implementation trial with two arms (NH chain and medical provider group). SETTING: A total of 27 community NHs in North Carolina that are typical of NHs statewide, conducted before announcement of the US Centers for Medicare and Medicaid Services antibiotic stewardship mandate. PARTICIPANTS: Nursing staff and medical care providers in the participating NHs. INTERVENTION: Standardized antibiotic stewardship quality improvement program, including training modules for nurses and medical providers, posters, algorithms, communication guidelines, quarterly information briefs, an annual quality improvement report, an informational brochure for residents and families, and free continuing education credit. MEASUREMENTS: Antibiotic prescribing rates per 1000 resident days overall and by infection type; rate of urine test ordering; and incidence of Clostridium difficile and methicillin‐resistant Staphylococcus aureus (MRSA) infections. RESULTS: Systemic antibiotic prescription rates decreased from baseline by 18% at 12 months (incident rate ratio [IRR] = 0.82; 95% confidence interval [CI] = 0.69‐0.98) and 23% at 24 months (IRR = 0.77; 95% CI = 0.65‐0.90). A 10% increase in the proportion of residents with the medical director as primary physician was associated with a 4% reduction in prescribing (IRR = 0.96; 95% CI = 0.92‐0.99). Incidence of C. difficile and MRSA infections, hospitalizations, and hospital readmissions did not change significantly. No adverse events from antibiotic nonprescription were reported. Estimated 2‐year implementation costs per NH, exclusive of medical provider time, ranged from $354 to $3653. CONCLUSIONS: Antibiotic stewardship programs can be successfully disseminated in community NHs through either NH administration or medical provider groups and can achieve significant reductions in antibiotic use for at least 2 years. Medical director involvement is an important element of program success. J Am Geriatr Soc 68:46–54, 2019 See related editorial by Furuno et al. in this issue. [ABSTRACT FROM AUTHOR]