A prospective, double-blind, placebo-controlled study was performed to determine the effectiveness of single-dose antibiotic prophylaxis in decreasing infectious complications after primary cesarean section. One hundred women at high risk for postoperative infectious morbidity were randomly assigned to receive either placebo or one 2-g dose of ceftizoxime at cord clamping. The incidence of endometritis in the antibiotic group was 6.0 versus 24.5% in the placebo group (P< .05). The incidence of febrile morbidity in the group receiving one dose of ceftizoxime was 14.0 versus 32.7% in the placebo group (P< .05). Single-dose ceftizoxime prophylaxis significantly reduced the incidence of endometritis and febrile morbidity in high-risk patients undergoing cesarean section.