BACKGROUND Postoperative choledochoscopy-related infection has been reported in the literature. We performed a prospective randomized trial to investigate the value of antibiotic prophylaxis for the prevention of such endoscopy-related infection. METHODS In a 2-year period from 1990 to 1991, 84 patients with biliary lithiasis were included in the study and randomized. Forty-four patients received antibiotic prophylaxis (1 gm cephalothin intravenously 30 minutes before the procedure and 500 mg cephalexin orally every 6 hours for 3 days afterward). Forty patients in the control group did not receive any antibiotics. RESULTS There was no significant difference between the groups in age, sex, preprocedure liver function, serum amylase level, white cell count, and duration of the procedure. The results of bacteriologic studies of the bile were also comparable in the two groups. One patient in the control group had transient chill and fever after the procedure. Two patients in the antibiotic group and one patient in the control group had mild abdominal pain. Mild hemobilia was noted in one patient in the antibiotic group. These complications were treated conservatively without any event. No difference was evident in the complications and the success of postoperative choledochoscopy between the two groups. CONCLUSIONS This prospective randomized study showed that routine antibiotic prophylaxis for postoperative choledochoscopy may be not necessary in selected conditions.