Background: Antibiotic resistance is a growing global health concern, largely driven by irrational and excessive antibiotic use. Antibiotic stewardship programs aim to optimize antimicrobial therapy, improve clinical outcomes, reduce resistance, and minimize healthcare costs.Objective: To evaluate the impact of antibiotic stewardship programs in tertiary hospitals on antibiotic utilization, prescription appropriateness, antimicrobial resistance patterns, and patient outcomes.Methods: A retrospective observational study was conducted among 350 hospitalized patients who received systemic antibiotics. Data regarding antibiotic prescriptions, culture reports, duration of therapy, de-escalation practices, hospital stay, treatment outcomes, and antimicrobial resistance trends were analyzed.Results: Appropriate antibiotic use was observed in 68.6% of cases after stewardship intervention compared with 42.3% before intervention. Culture-guided therapy increased from 36.0% to 61.4%. Antibiotic de-escalation was documented in 44.8% of eligible cases. Use of broad-spectrum antibiotics decreased from 58.2% to 39.5%. Average antibiotic duration reduced from 8.6 days to 6.2 days. Mean hospital stay decreased from 9.4 to 7.8 days. Multidrug-resistant isolates showed a modest decline after program implementation.Conclusion: Antibiotic stewardship programs significantly improve rational antibiotic use, promote culture-guided therapy, reduce unnecessary broad-spectrum antibiotic exposure, and contribute to better clinical outcomes. Regular audit, feedback, microbiological surveillance, and clinician education are essential components of effective stewardship.