The incidence of respiratory distress syndrome (RDS) in very preterm (gestational age < 32 weeks of gestation) infants is very high, ranging from 60 to 90%. The current understanding of its pathophysiology is that RDS has multifactorial etiology, of which surfactant deficiency remains the most important aspect. Despite advancements in respiratory support and surfactant administration methods, the important question of thresholds for surfactant administration remains vaguely answered. At present threshold for surfactant administration is largely based on clinical, radiological, blood gas parameters or a combination of them. Out of all the parameters, FiO2 is most commonly used as it is non-invasive and easier to titrate bedside. However, the currently available international and national guidelines which are based on FiO2 cut off doesn’t provide uniform cut off for FiO2 threshold prior to surfactant administration. The European Consensus guidelines on RDS management which is being widely followed for management of neonates with RDS recommends to provide surfactant at a FiO2 > 0.30 on CPAP pressure of at least 6 cm H2O. However, the evidence base for the recommendation is derived from a single retrospective study by Dargaville et al. (moderate quality, weak recommendation). Similarly, the currently released CPG India guideline for surfactant replacement therapy in neonates  recommends that surfactant may be given to preterm neonates < 34 weeks’ gestation with RDS stabilized on CPAP, who require a PEEP of > 6 cm H2O and a FiO2 > 0.30 (weak recommendation, expert consensus). These recommendations are strikingly in contrast to the findings of the two recently published network meta-analysis on FiO2 threshold for surfactant administration in preterm neonates which concluded that surfactant administration at a FiO2 cut of ³ 0.6 is not beneficial as it increases the risk of retinopathy of prematurity. It was further noted that among preterm neonates ≤30 weeks of gestation, FiO2 threshold of 40-45% was associated with lesser risk of mortality, and requirement of IMV (CoE: very low). Providing surfactant at fio2 threshold 0.3 as compared to 0.4 increases requirement of surfactant, its side effects ( hypoxemia ,desaturation, bradycardia ) and economic burden. However, majority of these findings are based on indirect evidence as there is a lack of controlled trial with direct comparison between the different FiO2 cut offs. Taking all the above facts together, it can be concluded that at present there is an equipoise regarding optimal FiO2 threshold for surfactant administration in preterm neonates. Therefore, this study was planned to compare whether administration of surfactant at a FiO2 threshold of 40% is non inferior as compared to its administration at 30% in preterm neonates between 26-32 weeks of gestational age.