To compare the efficacy of antibiotic prophylaxis through uterine lavage in women undergoing cesarean section in labor to the efficacy of the more standard, perioperative intravenous method, we prospectively randomized 100 women to receive either 2 g of cefotaxime in 1,000 mL of normal saline with a lavage protocol or 1 g of cefotaxime intravenously after cord clamping followed by 1-g doses 6 and 12 hours later. The two groups were similar with respect to age, gestational age, race, weight, length of labor and of ruptured membranes, use of internal monitoring, blood loss and number of vaginal examinations. Standard febrile morbidity and postpartum endomyometritis requiring antibiotic therapy occurred in 18% and 12%, respectively, of the lavage group and in 16% and 12%, respectively, of the intravenous group. Before the routine use of prophylactic antibiotics for cesarean section in labor on our service, the febrile morbidity and endomyometritis rates were 36% and 32%, respectively. The results confirm the benefit of prophylactic antibiotics for cesarean section in labor and demonstrate that the lavage and intravenous methods are similar with respect to efficacy.