Abstract
<jats:p>Background: Surgical antimicrobial prophylaxis (SAP) is a cornerstone of surgical site infection (SSI) prevention and represents one of the most cost-effective interventions in perioperative care. However, inappropriate antimicrobial selection, timing, dosing, and duration remain common, compromising clinical outcomes and increasing healthcare costs. This narrative review summarizes the pharmacoeconomic value of SAP and its role in antimicrobial stewardship, value-based healthcare, and healthcare sustainability. Methods: A narrative review was conducted to synthesize current evidence on the clinical and economic impact of SAP. The literature addressing the burden of SSIs, cost-effectiveness of prophylactic strategies, antimicrobial selection and duration, stewardship interventions, and future perspectives for optimizing perioperative infection prevention was reviewed. Results: Evidence consistently demonstrates that appropriate SAP reduces SSI rates, postoperative morbidity, hospital length of stay, readmissions, reoperations, and healthcare expenditures. First-generation cephalosporins, particularly cefazolin, remain the preferred agents for most procedures because of their efficacy, safety, and favorable pharmacoeconomic profile. In contrast, inappropriate antimicrobial selection and prolonged postoperative prophylaxis increase costs, antimicrobial consumption, adverse events, and antimicrobial resistance without improving outcomes. Antimicrobial stewardship programs significantly improve adherence to evidence-based recommendations, optimize antimicrobial use, and enhance both clinical and economic performance. Conclusions: Appropriate SAP is a high-value intervention that improves patient outcomes while reducing healthcare costs. Optimizing antimicrobial selection, timing, dosing, and duration through stewardship initiatives is essential to maximize clinical effectiveness, minimize unnecessary antimicrobial exposure, and promote sustainable healthcare systems. Future studies should incorporate standardized pharmacoeconomic methodologies to strengthen evidence-based decision-making and value-based surgical care.</jats:p>