Twenty-one women who underwent radical abdominal hysterectomy and pelvic lymphadenectomy were enrolled in a prospective, comparative, randomized, placebo-controlled clinical trial of antimicrobial prophylaxis. Preoperative endocervical flora was identified and was similar in pre- and postmenopausal private and clinic service women; 46% of the 119 preoperative isolates produced beta-lactamase enzyme. Women were given three doses of either placebo or cefoperazone plus sulbactam, an irreversible beta-lactamase enzyme inhibitor. Three women (27%) given placebo developed abdominal incision infections; one women given placebo also developed a pelvic infection. None given antibiotic developed operative site infection, but one women developed a drain site infection. A major operative site infection rate of 27% observed with placebo is high enough to warrant prophylaxis. Although antimicrobial prophylaxis at radical hysterectomy and pelvic lymphadenectomy eradicted operative site infection in our patient populations, a literature review indicates that individual determination of a requirement for prophylaxis is necessary.