OBJECTIVE: Surgical site infection (SSI) is one of the leading causes of hospital-acquired infection among hospitalized patients. It causes significant health problems and results in an extended length of hospital stay, increased cost, and increased patient morbidity and mortality. To prevent the development of SSI, surgical antibiotic prophylaxis (SAP) administration before surgery is an evidence-based practice. Therefore, this study aimed to assess the prevalence of SSIs and surgical antibiotic prophylaxis practice, and identifying the gap in practicing prophylactic surgical antibiotic use. METHODS: A retrospective cross-sectional study design was conducted on randomly selected 281 participants who fulfilled the inclusion criteria. Appropriateness of surgical antibiotic prophylaxis was assessed by clinical pharmacists based on the standard treatment guideline. Descriptive and multivariate logistic regression analyses were performed in SPSS version 25. Statistical significance was set at p <0.05. RESULTS: The overall prevalence of SSI was 19.6% (95% CI: 19-20.2). Majority of surgical patients (88.6%) got surgical antibiotic prophylaxis. Ceftriaxone and metronidazole (45.4%), and ceftriaxone (33.3%) were the most frequently used prophylactic antibiotics. Presence of comorbidity (AOR=9.18, 95% CI: 5.17-17.9, p<0.001), contaminated (AOR=6.01, 95% CI: 1.77-16.8, p=0.019) and dirty (AOR=7.20, 95% CI: 1.23-12.1, p=0.029) wound classes, devoid of prophylactic antibiotics (AOR=6.63, 95% CI: 0.89-19.3, p=0.006), the timing of prophylactic antibiotic administration between 1 hour and 2 hours before incision (AOR=8.2, 95% CI: 4.34-18.1, p=0.001), and 48 hours duration of surgical antimicrobial prophylaxis (AOR=7.20, 95% CI: 1.23-28.17, p=0.027) were significantly associated with the development of SSIs. CONCLUSION: The prevalence of SSI was relatively high despite most surgical patients were given prophylactic antibiotics. The presence of comorbidity, contaminated and dirty wound classes, devoid of prophylactic antibiotics, administering prophylactic antibiotics between 1 hour and 2 hours before incision, and 48 hours duration of surgical antibiotic prophylaxis were significantly associated with SSIs.