Effects of antibiotic stewardship program (ASP) interventions to optimize antibiotic use for infections in nursing home (NH) residents remain unclear. The aim of this systematic review and meta-analysis was to assess ASPs in NHs and their effects on antibiotic use, multi-drug-resistant organisms, antibiotic prescribing practices, and resident mortality. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic review and meta-analysis using five databases (1988-2020). Nineteen articles were included, 10 met the criteria for quantitative synthesis. Inappropriate antibiotic use decreased following ASP intervention in eight studies with a pooled decrease of 13.8% (95% confidence interval [CI]: [4.7, 23.0]; Cochran’s = 166,837.8, < .001, = 99.9%) across studies. Decrease in inappropriate antibiotic use was highest in studies that examined antibiotic use for urinary tract infection (UTI). Education and antibiotic stewardship algorithms for UTI were the most effective interventions. Evidence surrounding ASPs in NH is weak, with recommendations suited for UTIs.