Background: Surgical site infections are one of the most common causes of morbidity following surgery (SSI). The present study compared single dose prophylactic antibiotic versus empirical postoperative antibiotics in prevention of surgical site infections (SSI). Materials & Methods: 110 cases of clean and clean contaminated wounds of both genders were divided into 2 groups. Group I comprised of 55 patients who received a single dose of antibiotics half hour preoperatively. Group II (control) comprised of 55 patients who received post operative antibiotics after surgery for about 5-10 days. Parameters such as fever, swelling, hospital stay, pain, wound discharge, type of organism, SSI etc. was recorded. Results: Group I had 30 males and 25 females and group II had 27 males and 28 females. SSI was seen in 7 in group I and 11 in group II. Swelling was present in 10 in group I and 157 in group II and pain was present in 12 in group I and 18 in group II and fever was seen in 8 in group I and 16 in group II. The hospital stay was 1-3 days was 11 days in group I and 5 days in group II, 4-7 days in 32 in group I and 35 in group II and >7 days was 12 in group I and 15 in group II. Streptococcus viridans was isolated in 3 cases in group I and 5 cases in group 2 and Staphylococcus aureus in 4 cases in group I and 6 cases in group II. Wound discharge was serous in 4 in group I and 7 in group II and purulent in 3 in group I and 4 in group II patients. The difference was significant (P< 0.05). Conclusion: Prophylactic single-dose antibiotics have been demonstrated to be more effective in lowering hospital stays and surgical site infections than empirical post-operative therapy.