A unifactorial analysis for possible risk factors was applied to 2,700 consecutive operations for benign disease of the biliary tract. A series of high risk factors in relation to positive bacteriology and septic complication could be identified. These risk factors were patients who were elderly (>70 years;p<0.001), those who were diabetic, those who had a serum bilirubin >1.1 mg% (p<0.001), those who had acute cholecystitis (p<0.001), and those in whom choledochal stones were found (p<0.001). Using a multivariate analysis, we concluded that in patients with no risk factors (56.9%) the incidence of a positive bacteriology was low (10.9%) and they should receive no antibiotic prophylaxis. Patients with one risk factor (24%), had a 36% incidence of positive bacteriology and minimal pre-operative prophylaxis is recommended. Patients with two or more risk factors (19.1%) had a 77.6% incidence of positive bacteriology and full peri-operative prophylaxis is recommended, starting pre-operatively and continuing for 3 to 5 days postoperatively. The aim of this study was to identify patients at risk for septic complication in biliary surgery and to create new guidelines for the antibiotic treatment of selected groups.