The effectiveness of perioperative Piperacillin for prevention of operative-site infection after gynaecological surgery was studied in a total of 100 patients. In an open randomized clinical trial of 52 women undergoing abdominal or vaginal hysterectomy Piperacillin was compared to the combination Gentamicin/Metronidazole. Piperacillin was well-tolerated. Surgical-site infection was diagnosed in the Piperacillin group in two patients and in the Gentamicin/Metronidazole group in one patient. The occurrence of postoperative febrile morbidity was also similar between the two group. In 48 patients undergoing complicated gynecological surgery of long duration, only Piperacillin was administered perioperatively. Thirty-five of these 48 women underwent oncological operations and the mean operative length was 3.3 h. One patient developed a transient rash after the administration of Piperacillin. No other adverse side-effects were observed. Nine of these 48 patients developed a surgical-site infection postoperatively, and this was found to be significantly more often than in the first group of 52 patients. It was concluded that Piperacillin seems to be a valuable alternative for perioperative prophylaxis in gynecological surgery. Its effectiveness in vaginal and abdominal hysterectomy is similar to the combination of Gentamicin/Metronidazole, but after complicated surgery of long duration a decreased effectiveness should be reckoned with.