A three year prospective randomised study was undertaken to study the efficacy of three regimens of antimicrobial drug combinations in reducing postoperative wound sepsis in acute appendicitis. Group A--Metronidazole and gentamicin; Group B--Metronidazole and ciprofloxacin; Group C--Metronidazole and cefotaxime. Randomization was done by drawing from a set of sealed envelopes. Antibiotics were started preoperatively once a presumptive diagnosis of appendicitis was made, provided there was no history of prior antibiotic usage. For simple appendicitis (normal or inflamed) two more doses were given postoperatively. For complicated appendicitis, duration of antibiotic treatment was four days postoperatively. All antibiotics were given intravenously to avoid variations in bioavailability. Wound was inspected daily till discharge and at 30 days post operatively or earlier if the patient had symptoms of wound infection. A total of 128 patients completed the study. Eighty nine were simple appendicitis while the rest were complicated. Twenty one developed wound infection. Out of 21, 13 occurred in group A, 5 in group B and 3 in group C. Individually, the difference in infection rates between group A and group C patients with simple appendicitis was statistically significant. Infection rates in all other groups were not statistically different. Cefotaxime and metronidazole combination had the lowest wound infection rate. Hence it is recommended for antibiotic prophylaxis.