A randomized trial of intrapartum versus postpartum antibiotic treatment of women with intra-amniotic infection was conducted. Intra-amniotic infection was treated with ampicillin and gentamicin during labor (at the time of diagnosis) in 26 women and immediately after umbilical cord clamping in 19 women. Intrapartum treatment led to a lower incidence of neonatal sepsis (0 versus 21%; P = .03) and a shorter neonatal hospital stay (3.8 versus 5.7 days; P = .02) when compared with postpartum treatment. There were no significant differences in the microbiologic results, the gestational age, or the birth weight between the groups. Intrapartum-treated mothers had a shorter mean postpartum stay, a lower mean number of febrile days, and a lower mean peak postpartum temperature than did postpartum-treated mothers; these differences were all statistically significant (P = .05). The treatment of clinical intra-amniotic infection during labor results in improved outcome.