We conducted a prospective, double-blind, randomized, placebo-controlled study of cefoxitin perioperative prophylaxis in 386 women having cesarean sections after labor or rupture of membranes. Private patients constituted 70% of subjects. Cefoxitin was chosen for its low toxicity and its broad spectrum against common obstetric pathogens including Bacteroides fragilis. Cefoxitin-treated women received 2 mg of drug intravenously at umbilical cord clamping and at 6 and 12 hours after surgery. Demographic and obstetric variables did not differ between the 190 placebo-treated women and the 196 cefoxitin-treated women. The morbidity rate from infection was significantly reduced by cefoxitin prophylaxis. Seven factors were significantly correlated with increased risk of infection after cesarean section: maternal age, socioeconomic status, race, gestational age, duration of internal fetal monitoring, use of intrauterine pressure catheter, and obesity. Cefoxitin prophylaxis resulted in significant decreases in infection incidence in women with one, two, and three risk factors, respectively, but the reduction was not significant in women with no risk factors. Length of hospital stay was not significantly reduced by cefoxitin prophylaxis but antibiotic use was decreased 24%.