Surgical site infections (SSIs) are a significant concern in global healthcare, particularly in middle and low-income countries, leading to increased hospitalizations, morbidity, mortality, and financial strain. Ranked third in the CDC's National Nosocomial Infections Surveillance System, SSIs have prompted a focus on preventive measures, notably surgical antimicrobial prophylaxis (SAP). However, SAP is often used inappropriately, contributing to the rise of Antimicrobial Resistance (AMR). Addressing this, a six-month prospective observational study was conducted in a tertiary care hospital to assess the adherence to SAP guidelines among 386 patients undergoing surgeries in various specialties. The study aimed to evaluate the appropriateness of SAP practices and identify factors leading to non-compliance. Results showed that only 58.3% of patients fully adhered to the guidelines. While 100% compliance was observed in SAP indication, lower adherence was noted in the timing of administration (97.7%), choice of SAP (85%), and duration of prophylaxis (70.2%). These findings underscore a significant gap between recommended SAP practices and actual implementation. This gap highlights the need for stronger Institutional Antimicrobial Stewardship (AMS) programs and the critical role of clinical pharmacists in regularly evaluating SAP and prescribing practices. To combat the rise of antibiotic resistance while ensuring patient safety, enhancing SAP practices in line with national and international recommendations is essential. The study advocates for more active interventions at the time of order to optimize antibiotic use, thereby addressing the challenge of compliance in SAP guidelines.