Objective: To study the association between antenatal exposure to chorioamnionitis and the neonatal response to surfactant. Study design: Prospective observational cohort of 301 preterm infants of gestational age ≤ 32.0 weeks, 146 of whom received surfactant according to standardized criteria. Fraction of inspired oxygen (FiO2) requirement (using analysis of variance) and time to extubation (using Kaplan-Meier and Cox regression analyses) were compared between groups based on the presence of histological chorioamnionitis (HC) with or without fetal involvement (HC-, n = 88; HC + F-, n = 25; HC + F+, n = 33) and between infants who developed bronchopulmonary dysplasia (BPD) or died (n = 57) and BPD-free survivors (n = 89). Multiple logistic regression was performed to investigate the association between HC and BPD. Results: Compared with HC- infants, HC + F+ infants had significantly greater FiO2 requirement and prolonged time to extubation postsurfactant, not accounted for by differences in gestational age and birth weight. Infants with BPD/death had a strikingly similar pattern of increased FiO2 requirement postsurfactant. Moreover, in infants who received surfactant, HC + F+ status was associated with increased risk for BPD (odds ratio [OR] = 3.40; 95% confidence interval [CI] = 1.02-11.3; P = .047) and for BPD/death (OR = 2.72; 95% CI = 1.00-7.42; P = .049). Conclusions: An impaired surfactant response was observed in preterm infants with severe chorioamnionitis and may be involved in the association between chorioamnionitis, mechanical ventilation, and the development of BPD.