To compare two treatment strategies in preterm infants with or at risk of respiratory distress syndrome: early surfactant administration (within one hour of birth) versus late surfactant administration, in a geographically defined population.The primary outcome was chronic lung disease (CLD) and mortality before/at 36 weeks. Secondary outcomes included: duration of mechanical ventilation and continuous positive airway pressure (CPAP), post-natal steroids for CLD and major neonatal morbidities.Premature infants born at 22-32 weeks' gestation between January 2006 and December 2009.Ten neonatal intensive care units (NICUs) in New South Wales (NSW) and Australian Capital Territory (ACT), Australia.Retrospective analysis of prospectively collected data from the regional NICU database in NSW and ACT.Of the 2170 infants who received surfactant, 1182 (54.5%) and 988 (45.5%) received early and late surfactant, respectively. The early surfactant group was less mature (27.1 ± 2.1 versus 29.4 ± 2.1 weeks) and had more CLD and mortality (40.2% versus 20.0%). The multivariable analysis showed early surfactant to be associated with less duration of ventilation, longer duration of CPAP and longer hospital stay but had little or no impact on CLD/mortality.Early surfactant administration is associated with shorter duration of ventilation but does not appear to be significantly protective against CLD/mortality among premature infants. This may support the growing evidence for consideration of CPAP as an alternative to routine intubation and early surfactant administration. Further investigation from large randomized clinical trials is warranted to confirm these results.