Background: Pre-operative single dose antibiotic prophylaxis has shown to reduce the incidence of surgical site infections and thereby patient morbidity. Aims: To evaluate effectiveness of single dose antibiotic prophylaxis in clean surgeries at a tertiary care hospital. Material and Methods: A total of 72 patients undergoing clean surgeries were included after they satisfied the inclusion and exclusion criteria. Results: Single dose of an intravenous prophylaxis of ceftriaxone in clean surgeries excisional biopsy of lipoma, dermoid cyst, sebaceous cyst, enucleation of fibroadenoma, herniotomy, eversion of hydrocele etc. was efficacious in preventing surgical site infection. Surgical site infection was associated with patient’s age, lower haemoglobin levels and longer hospital stay in 3 out of 72 patients. Conclusion: In the present study it was observed that prophylactic single shot of antibiotic is efficacious in averting surgical site infection and is economical for patients undergoing clean surgeries. Factors associated with surgical site infection were patient’s age, haemoglobin and associated co-morbidity like diabetes.