The purpose of this study was to elucidate whether the use of intravenous ampicillin (vs. placebo therapy) in women in early active-phase preterm labor reduces infectious complications postpartum in mothers and their newborns. A randomised, double-blind, placebo-controlled study was carried out on 102 women with gestational age < 37 completed weeks in the active phase of labor (dilatation of cervix ≧ 4 cm). Enrolled women received a loading dose of 5 g of ampicillin (n = 44) or placebo (n = 58) in intravenous infusion twice, 4 h apart. In a few cases, this interval was shortened in order to obtain a minimum interval of 1 h between the last dose and delivery. There was a significant reduction in the ampicillin group (vs. the placebo group) of the prevalence of neonatal infection (OR 19.0; 95% CI 5.5–80.8), histological chorioamnionitis (OR 5.9; 95% CI 2.0–19.4) and puerperal endometritis-myometritis (OR 3.7; 95% CI 1.3–10.3). It is concluded that women in the active phase of preterm labor and their newborns benefit from treatment with intravenous ampicillin. Antibiotic treatment reduces the incidence of neonatal infectious morbidity, of puerperal endometritis and of histological chorioamn