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Background and Aim: Respiratory distress syndrome (RDS) is one of the most common causes of morbidity and mortality in preterm neonates, and is caused by surfactant deficiency. Among different strategies for treatment of RDS, the INSURE method (Intubation, Surfactant, Extubation to NCPAP) has some advantages over the mechanical ventilation with surfactants administration. This study was conducted to determine the efficacy of INSURE method in NICU of Mahdieh Hospital, during 2007-8. Materials and Methods: In this study, 66 preterm infant with gestational age of 25 to 32 weeks and birth weight of 600 to 1500 gram who had clinical sign of moderate to server RDS were included. These infants received surfactant by INSURE method (surfactants administration via endotracheal tube during 2-3 min and then extubation to NPCPAP). Results: INSURE success rate was 60.6% and proved to be gestational age (p= 0.019) and birth weight (p< 0.001) dependent. In the INSURE success group, the need for second dose of surfactant (p< 0.001), mean duration of hospital stay (p= 0.035), complication of disease (p< 0.001) and death (p< 0.001) were less than the INSURE failure group. However no significant difference in gender, method of delivery, parity and age of surfactants administration were seen among the groups. ‍Conclusion: The INSURE method reduces the use of mechanical ventilation, complications, duration of hospital stay and death in neonates with RDS.