SETTING: A referral hospital in Kavre, Nepal. OBJECTIVES: To assess 1) compliance with National Antibiotic Treatment Guidelines (NATG), specifically, whether the administration of surgical antibiotic prophylaxis (SAP) (initial dosing and redosing) was in compliance with NATG for patients who were and were not eligible, and 2) development of surgical site infections (SSIs) among patients who underwent surgery in the Department of General Surgery (July–December 2019). DESIGN: This was a retrospective cohort analysis. RESULTS: The analysis included 846 patients, of which 717 (85%) patients were eligible for SAP and 129 (15%) were ineligible. Of those eligible, 708 (99%) received the initial dose; while 65 (50%) of the ineligible did not receive any dose. Of those who received the initial dose, 164 (23%) were eligible for redosing. Of these, only 23 (14%) received at least one redosing and 141 (86%) did not receive it. Overall compliance with NATG was achieved in 75% (632/846) of patients. SSIs occurred in 23 (3%) patients, 8 (35%) of whom did not have SAP administered according to NATG. CONCLUSION: A relatively high overall compliance with NATG for SAP administration was reported. Recommendations were made to improve compliance among those who were ineligible for SAP and those who were eligible for redosing.