© 2018 Elsevier Inc. Objectives: We examined the impact of prenatal exposure to maternal antibiotics on risk of necrotizing enterocolitis (NEC), late onset sepsis (LOS), and death in infants born preterm. Study design: Secondary data analysis was conducted via an extant cohort of 580 infants born <32 weeks of gestation and enrolled in 3 level III neonatal intensive care units. Prenatal antibiotic exposure was defined as antibiotics received by the mother within 72 hours before delivery. Postnatal empiric antibiotic exposure was defined as antibiotic initiated within the first day of life without documented infection, categorized as low (<5 days) or high (>5 days) duration. Results: Two-thirds of mothers received antibiotics within 72 hours before delivery, of whom 59.8% received >1 antibiotic. Ampicillin (37.6%) and azithromycin (26.4%) were the most common antibiotics given. NEC occurred in 7.5%, LOS in 11.1%, death in 9.6%, and the combined outcome of NEC, LOS, or death in 21.3% of study infants. In multiple logistic regression models adjusted for gestational age, postnatal empiric antibiotic exposure, and other factors, prenatal antibiotic exposure was associated with reduced risk of NEC (OR 0.28; 95% CI 0.14-0.56; P <.001), death (OR 0.29; 95% CI 0.14-0.60; P =.001), but not LOS (OR 1.59; 95% CI 0.84-2.99; P =.15), although protection was significant for the combined outcome (OR 0.52, P <.001). High postnatal empiric antibiotic exposure was associated with greater risk of death but not other outcomes in multiple regression models (OR 3.18, P =.002). Conclusions: Prenatal antibiotic exposure was associated with lower rates of NEC or death of infants born preterm, and its impact on infant outcomes warrants further study.