Inappropriate antibiotic prescribing remains a major challenge for antimicrobial stewardship, partic-ularly in secondary-care hospitals. This study evaluated the association between a nurse-led antimi-crobial stewardship intervention and inappropriate prescribing in a hospital in Mexico. A prospec-tive, quasi-experimental before-and-after study without a control group was conducted across 27 weekly reporting periods in 2026. A total of 458 antibiotic prescriptions from 390 hospitalized pa-tients were assessed using predefined clinical criteria. Multivariable logistic regression incorporated patient-clustered robust standard errors. Inappropriate prescribing decreased from 51.97% (119/229) before the intervention to 37.12% (85/229) afterward (absolute difference, −14.85 percentage points; p = 0.0014). The adjusted odds ratio was 0.544 (95% CI, 0.368–0.804). Nurses reviewed 95.63% of post-intervention prescriptions, and 79.55% of communicated recommendations were fully or par-tially accepted. Mean antibiotic treatment duration decreased from 7.05 to 6.18 days (p < 0.001). The intervention was associated with less inappropriate antibiotic prescribing and shorter treatment du-ration, although the uncontrolled design precludes causal attribution.