A double-blind randomized trial of antibiotic prophylaxis was performed with 49 patients undergoing extended pelvic surgery for adenocarcinoma of the endometrium. In this series infections of the Hemovac drain site(s) were most common (8 of 10 infections); only 1 serious infection, pelvic cellulitis, occurred. Short-term perioperative cefamandole therapy significantly reduced infections and febrile morbidity in these patients as compared with patients who received a placebo. The average postoperative hospital stay for patients in the cefamandole group was 1 day less than for patients in the placebo group, but the difference was not statistically significant. The presence of 10 colony-forming units or more of a potential pathogen in lymph fluid collected through the Hemovac drains correlated with clinical infection. The low incidence of serious infection in this study precludes any conclusion regarding the impact of antibiotic prophylaxis in preventing serious infection after operation for gynecologic malignancy.