OBJECTIVE: Our purpose was to determine whether a single postpartum dose of a cephalosporin would effectively treat women with intrapartum chorioamnionitis and decrease the length of hospitalization. STUDY DESIGN: After vaginal delivery consenting women who had received antibiotics for chorioamnionitis were assigned to postpartum treatment with either a single 2 gm intravenous dose of cefotetan or to cefotetan 2 gm given intravenously every 12 hours for a minimum of 48 hours. Chorioamnionitis was defined as an intrapartum temperature of ≤100.4°F and maternal or fetal tachycardia, maternal leukocytosis, or uterine tenderness. Patients were discharged when they had received their assigned dosage of cefotetan, were afebrile (temperature <100.4°F) and ≤24 hours from delivery. RESULTS: We studied 109 women (55 single dose, 54 multiple dose) with chorioamnionitis. The two groups were similar with regard to demographic and intrapartum characteristics. The median (range) interval from delivery to discharge was 24 hours lower in the single-dose group (33 [16 to 190] vs 57 [36 to 190] hours, p = 0.0001). The incidence of failed therapy was similar (single dose: 6/55, 11%, vs multiple dose: 2/54, 3.7%, p = 0.27). CONCLUSIONS: A single postpartum dose of cefotetan appears to be effective treatment for intrapartum chorioamnionitis after a vaginal delivery and decreases the length of hospital stay.