The role of prophylactic cefotaxime and a combination of ampicillin and tinidazole was assessed in 201 patients undergoing hysterectomy. One hundred and twenty-five patients were evaluated in the abdominal hysterectomy group and 46 patients completed the protocol after vaginal hysterectomy. Patients were allocated randomly to receive either (1) no prophylactic antibiotic, (2) cefotaxime peroperatively for 24 h or (3) ampicillin/tinidazole peroperatively for 24 h. Both cefotaxime and ampicillin/tinidazole reduced the septic complication rate in abdominal and vaginal hysterectomy. Efficacy was most evident in reducing early urinary infections after abdominal hysterectomy (0.001<p<0.01). Cefotaxime and ampicillin/tinidazole were equally effective and no significant side-effects were demonstrated. Cefotaxime is recommended as a safe and effective agent for hysterectomy prophylaxis.