BACKGROUND Some clinicians administer prophylactic antibiotics routinely before laparoscopic cholecystectomy, and the results of some of the studies in the literature support this practice. We conducted a prospective randomized trial to determine whether administration of prophylactic antibiotics is necessary during routine laparoscopic cholecystectomy in low-risk patients. METHODS Two hundred fifty patients without evidence of acute inflammation, common duct stones, or other indications for antibiotics were randomized to receive three perioperative doses of cefazolin or no prophylaxis and followed up for complications up to 30 days postoperatively. The primary end point was the occurrence of a major infectious complication, defined as that causing a systemic response, delaying discharge, or leading to readmission. Minor infectious problems were also noted, defined as those causing local symptoms only. RESULTS One hundred twenty-eight patients were randomized to receive prophylactic antibiotics (PA group), 122 to receive none (NONE group; two patients in this group were actually given preoperative antibiotics). Only one major complication occurred (in a patient in the NONE group), an abscess in the presence of a bile leak, despite the administration of antibiotics when the leak was discovered several days before infectious problems arose. There were four minor problems: two lower urinary tract infections and one superficial wound infection in a NONE patient and one urinary tract infection in a PA patient (not significant); all were easily managed. The prophylactic antibiotics did not sterilize the bile, and infectious complications were not associated with weight, inflammation found at the time of operation, reported stone or bile spill-age, or conversion to open operation. CONCLUSIONS Prophylactic antibiotics are not necessary for elective laparoscopic cholecystectomy in low-risk patients.