The high burden of antimicrobial resistance in India necessitates the urgent implementation of antimicrobial stewardship programs (ASPs) in all healthcare settings in India. Most ASPs are based at tertiary-care centers, with sparse data available regarding the effectiveness of an ASP in a low-resource primary/secondary-care setting. We adopted a hub-and-spoke model to implement ASPs in 4 low-resource, secondary-care healthcare settings. The study included 3 phases measuring antimicrobial consumption data. In the baseline phase, we measured days on antimicrobial therapy (DOTs) with no feedback provided. This was followed by the implementation of a customized intervention package. In the postintervention phase, prospective review and feedback were offered by a trained physician or ASP pharmacist, and days of therapy (DOT) were measured. In the baseline phase, 1,459 patients from all 4 sites were enrolled; 1,233 patients were enrolled in the postintervention phase. Both groups had comparable baseline characteristics. The key outcome, DOT per 1,000 patient days, was 1,952.63 in the baseline phase and significantly lower in the post-intervention period, at 1,483.06 (P = .001). Usage of quinolone, macrolide, cephalosporin, clindamycin, and nitroimidazole significantly decreased in the postintervention phase. Also, the rate of antibiotic de-escalation was significantly higher in the postintervention phase than the baseline phase (44% vs 12.5%; P < .0001), which suggests a definite trend toward judicious use of antibiotics. In the postintervention phase, 79.9% of antibiotic use was justified. Overall, the recommendations given by the ASP team were fully followed in 946 cases (77.7%), partially followed in 59 cases (4.8%), and not followed in 137 cases (35.7%). No adverse events were noted. Our hub-and-spoke model of ASP was successful in implementing ASPs in secondary-care hospitals in India, which are urgently needed.