Objective. To determine whether the introduction of surfactant therapy was associated with decreased mortality for high-risk preterm neonates weighing 601 to 1300 g at birth. Design. Before-after observational study. Setting. Eight tertiary care neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. Patients. The outcomes for neonates with birth weight 601 to 1300 g admitted in the 2 years before surfactants became available (n = 2780) were compared with those of neonates admitted in the year beginning 2 months after surfactants became available (n = 1413). Main outcome measures. The primary outcome measure was in-hospital mortality; secondary outcome measures included durations of assisted ventilation, length of hospitalization, and neonatal morbidity. Results. Forty percent of neonates in the postsurfactant group received surfactant (range 28% to 69% at the centers). Mortality decreased from 27.8% before to 19.9% after surfactant therapy was introduced (Mantel-Haenszel χ2 = 31.4, P = .001). The adjusted odds ratio for mortality after surfactants became available was 0.73 (95% confidence interval 0.55 to 0.95). The duration of assisted ventilation and length of hospitalization increased after surfactants were introduced (P = .0001 for both outcomes). Conclusion. Mortality for neonates weighing 601 to 1300 g decreased after surfactant therapy was introduced, suggesting that the efficacy of surfactants demonstrated in randomized controlled trials will translate into effectiveness in routine clinical care.