Objectives: This study examined the effects of intrauterine cocaine exposure on very low birth weight infants with respect to their surfactant requirement and need for ventilatory support. Study Design: A retrospective cohort study was conducted on infants with birth weight between 750 and 1500 g admitted to the neonatal intensive care unit between January 1992 and January 1995. Results: Of the 149 infants studied, 48 infants were exposed only to cocaine and 101 infants had no drug exposure. There were no significant differences between the two groups for gestational age, sex, abruptio placenta, prolonged rupture of membranes, and antenatal steroid usage. The cocaine-exposed group had a significantly greater birth weight (1190 vs. 1109, p < 0.02), less prenatal care (48% vs. 14%, p < 0.00007), older maternal age (30 vs. 24, p < 0.00002), more black race (79% vs. 57%, p < 0.01), and more rapid plasma reagin (RPR) positivity (25% vs. 2%, p < 0.00006). There were no significant differences in median APGAR scores, or incidence of necrotizing enterocolitis, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), and bronchopulmonary dysplasia (BPD) between the two groups. Cocaine-exposed infants received surfactant treatment less often (73% vs. 48%, p < 0.0035), received fewer mean doses of surfactant (0.4 vs. 10.0, p < 0.0014), and were intubated less frequently (44% vs. 65%, p < 0.012). There was no significant difference between groups for intubation at 24 and 48 hours and for the development of bronchopulmonary dysplasia. Conclusion: Perinatal cocaine exposure appears to have some significant short-term effects on the need for surfactant replacement therapy and need for initial intubation in respiratory distress syndrome (RDS) but no overall effect on the development of BPD.