Objective: To compare the efficacy of two surfactants, Exosurf Neonatal(Burroughs Wellcome Co.) and Survanta (Ross Laboratories), for the treatment of neonatal respiratory distress syndrome. Design: Multicenter randomized trial. Setting: Eleven tertiary care university neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. Patients: Newborn infants (n=617) weighing 501 to 1500 gm with respiratory distresssyndrome who were receiving assisted ventilation with 30% oxygen or more within 6 hours of birth were enrolled between January 1991 and January 1992. Interventions: Infants were randomly assigned to receive up to four intratrachealdoses of either Exosurf Neonatal (n=309) or Survanta (n=308). Main outcome measures: The occurrence of death or bronchopulmonary dysplasia 28 days after birth and the average fraction of inspired oxygen (Fio2) and mean airway pressure (MAP) during the first 72 hours after treatment. Results: Death or bronchopulmonary dysplasia occurred in 67% of the infants in the Exosurf group and 62% of those in the Survanta group (adjusted relative risk, 1.07; 95% confidence interval, 0.96 to 1.20). During the 72 hours after the first surfactant dose, the average Fio2 (±SEM) was 0.50±0.01 for Exosurf and 0.42±0.01 for Survanta (difference, 0.08; 95% confidence interval, 0.05 to 0.11); the average MAP (±SEM) was 7.64±0.21 cm H2O for Exosurf and 6.93±0.21 cm H2O for Survanta (difference, 0.71 cm H2O; 95% confidence interval, 0.13 to 1.29 cm H2O). There was no difference between the groups in the incidence of other neonatal morbidities or in the duration of hospitalization, assisted ventilation, or supplemental oxygen administration. Conclusion: We found no difference between treatment groups in the incidence of death or bronchopulmonary dysplasia, although we did observe a difference in the initial response to treatment as measured by Fio2 and MAP. © 1993 Mosby-year book, Inc.