Background: Healthcare-Acquired Infections (HAIs) are serious healthcare complications affecting hospital stay, in-hospital mortality, and costs. Root cause analysis has identified the inappropriate use of antibiotics as the main causative factor in the expansion of multi-drug-resistant organisms (MDRO) in our hospital. An Antimicrobial Stewardship (AMS) program was implemented to optimize antibiotic use, limit the development of resistance, improve therapeutic efficacy and clinical outcomes, and reduce costs. Methods: The stewardship strategies were: antimicrobial oversight on “critical” antibiotics; the development of hospital guidelines on antibiotic selection with the production of a consensus document; the implementation of clinical and management control algorithms with visual impact and Business Intelligence methods; training and updating; and the monitoring of outcome measures and process indicators. Results: Clinical outcomes: length of stay reduced by 0.23 days, hospital readmission/first month rates decreased by 19%, and mortality for infections reduced by 8.8%. Microbiological Outcomes: Clostridium Difficile colitis incidence reduced by 9.1%.Economic Outcomes: Reduction in antimicrobial costs by 35% on average fee/discharged patient. Conclusions: The systematic application of the AMS program in a small hospital led to multiple improvements in clinical, microbiological, and economic outcome measures. The analysis of the core indicators for our hospital AMS program showed a significant adherence to the model and hospital recommendations.