In this double-blind prospective randomized trial, our objective was to investigate the effect of antibiotic prophylaxis in patients undergoing elective inguinal hernia surgery with mesh repair in a large-volume tertiary referral trauma center. Eligible patients were assigned randomly to either an antibiotic prophylaxis group or a control group. Patients in the prophylaxis group were given 1 g cefazolin by IV bolus injection whereas the placebo control group received an equal volume of sterile saline preoperatively. A Lichtenstein repair was done in all cases. The patients were examined for surgical site infection (SSI) and other postoperative local complications before discharge, and reexamined 3, 5, 7, and 30 days after discharge. Groups were well matched for age, sex, coexisting diseases, ASA scores, type of hernia, type of anesthesia, duration of surgery. Incidence of infection was 7% in the control group (7/100) and 5% in the prophylaxis group (5/100) (P = 0.38). All the infections were superficial and responded well to drainage and proper antibiotic therapy. All other postoperative complications were similar in the two groups. In our settings antibiotic prophylaxis has no significant effect on the incidence of SSI in elective repair of inguinal hernias with mesh. The most effective way to reduce the incidence of infection in prosthetic repair may be a specific center for treatment of abdominal wall hernias.