PURPOSE: This study was performed to investigate the effectiveness and safety of the prophylactic administration method of surfactant, followed by rapid extubation to nasal CPAP (nCPAP) in very preterm infants. METHODS: Thirty-three preterm infants with 24-29 weeks gestational age (GA) were treated with the method of prophylactic administration of surfactant by a brief intubation within 15 minutes after birth and rapid extubation to nCPAP for the treatment of respiratory distress. The variables and complications related to oxygen therapy and mechanical ventilation (MV) were compared with those of 24 historical control infants with comparable GA, treated with the rescue surfactant administration with prolonged MV for the respiratory distress syndrome (RDS). RESULTS: Prophylactic surfactant with nCPAP did not reduce the total durations of oxygen therapy and MV, compared with the rescue surfactant with MV (P=0.622 P=122, respectively). The incidence of death and BPD at 36 weeks postmenstrual age (PMA) and other complications related to oxygen therapy and MV were not increased in the infants treated with prophylactic surfactant with nCPAP despite the lower GA and birth weight. In the subgroup analysis for infants with 27-29 weeks of GA, the total duration of MV tended to decrease in infants treated with prophylactic surfactant with nCPAP (Odd ratio, 0.93, 95% Confidence interval, 0.87, 1.00, P=0.051). CONCLUSION: Prophylactic surfactant administration followed by rapid extubation to nCPAP tended to reduce the duration of MV in infants with GA of 27-29 weeks, compared with the rescue surfactant administration with prolonged MV for RDS.