Introduction: Respiratory Distress Syndrome (RDS) is a common cause of mortality and morbidity in preterm. It is the commonest indication for ventilation in neonates in India. Surfactant Replacement Therapy (SRT) for RDS is a major breakthrough that has revolutionized the survival of premature infants worldwide. Randomized controlled trials have also demonstrated that prophylactic or early surfactant therapy compared with delayed surfactant treatment results in improved outcomes for preterm infants at high risk. Objective: To assess the outcome of early and late rescue surfactant administration by InSuRE (Intubation, Surfactant and Rapid Extubation) technic in managing preterm neonates with respiratory distress syndrome (RDS). Methodology: Study design: Prospective analytical study. Sample size: 144 preterm babies between 28-34 weeks of GA. Setting: Level III NICU at SVRR Government General Hospital, Tirupati, AP. Study Period: 1 year (Sep 2013 to Aug 2014). Method: All preterm babies between 28-34 weeks with respiratory distress were given surfactant with InSuRE technic immediately and categorized into early and late rescue group depending on the time of surfactant therapy i.e. within 2 hrs. of life and between 2-24 hrs. of life respectively. Results: In early rescue group there is significant reduction in mortality and lessen the need of mechanical ventilation with p value <0.05. Conclusion: Early routine surfactant administration within 2 hrs. of life as compared to late selective administration significantly reduced the need mechanical ventilation within 7th day of life and mortality among preterm with respiratory distress syndrome.