Background: The role of prophylactic antibiotics in preventing surgical site infection (SSI) after surgeries like gastrointestinal, Orthopedics, and plastic surgical procedures are quite well known, although their efficacy in clean, elective major surgeries are still debatable. An effective antimicrobial prophylaxis that providing coverage throughout the entire procedure, not only reduces the risk of surgical site infections, but also of complications associated with it. Various studies have shown that appropriately-timed “single shot” antibiotic prophylaxis is as effective as multiple-dose prophylaxis. Aim: To assess the efficacy of single dose prophylactic antibiotics in preventing SSI after clean, elective surgery. Materials and methods: Patients planned for clean, elective surgeries were included in a prospective study which was conducted for a year in a tertiary centre. Post operatively, the patients were then assesses. Results: Of the total 100 cases, 55 patients belonged to the female gender and 45 cases belonged to male gender. In this study, maximum number of patients belonged to the age group of 26 to 50 years, 48 cases belonged to 51 to 75 years, and single case belonged to the age group less than 25 years. Regarding the complication developed post surgically 7 cases were observed to develop purulent discharge from the surgical site and about 7 other cases developed seroma and discharge. Of the 100 cases, 4 cases were discharged on the first postoperative day, 86 patients were discharged on second or third post operative day. The rest were discharged on subsequent days. Conclusion: Recent developments in the antibiotic prophylaxis, including the initial time of antibiotic administration, proper choice of antibiotic agent that cover all possible infective agents, the short duration of antibiotic treatment have proved to improve the efficacy of these drugs in surgical settings. A systemic regimen of a single dose of an appropriately selected cephalosporin given during the immediate preoperative period is safe and effective in clean elective surgeries.