In addition to surfactant deficiency, increase of lung fluid content and secretion of fluid derived from the blood participate in the pathogenesis of RDS in newborns. We hypothesized that the administration of salbutamol (β-agonist) to increase lung fluid absorption would decrease the INSURE failure rate in newborns with respiratory distress syndrome (RDS) treated with intratracheal surfactant. Design Blinded, randomized clinical trial study. Setting/population Level III NICU, premature infants with RDS requiring intratracheal Surfactant. Forty Eight newborns with RDS treated with intratracheal Surfactant were randomized into two groups as Group A, Normal saline (as control group) and Group B (intervention group), Salbutamol were administered intratracheally in addition to Surfactant. Intubation-Surfactant administration- Rapid Extubation (INSURE) failure rate as primary outcome and secondary outcome as follow: duration of the need to NCPAP, mechanical ventilation and oxygen therapy; complications (patent ductus arteriosus, pneumothorax); mortality (respiratory or prematurity related complication) and the duration of hospitalization were assessed. Twenty Four patients in each group were studied. INSURE failure was seen in16 (66.7 %) and 10 (41.7 %) of normal saline and salbutamol groups respectively (p = 0.082). The duration of NCPAP in control group was 69.5 ± 54.9 h while in Salbutamol group was 51.6 ± 48.7 h (p = 0.316). All of deaths were related to respiratory failure. No differences in mortality or complications of RDS were observed. The duration of hospitalization was longer in control group than interventional group, 28.3 ± 18.1 and 18.6 ± 8.6 days, respectively. (p = 0.047). Salbutamol may improve the clinical course of newborns with RDS requiring Surfactant. IRCT2014072714215N1