Background: Respiratory distress syndrome (RDS) considered a major problem in preterm infants. Surfactant deficiency is the main cause of RDS as it is necessary for lung functions. The treatment of Surfactant in neonatology reduced mortality and improveed the prognosis of the respiratory distress syndrome (RDS). Aim and objectives : To compare between efficacies of surfactant administration by laryngeal mask technique and minimally invasive surfactant therapy (MIST). patients and methods : A randomized clinical trial study was carried out at hhe NICU, Zagazig University Hospitals, on 24 patients that were divided into two groups, All patients received (poractant 120 mg/1.5 mL) and the same dose (200 mg/kg) for surfactant preparation, close monitoring of the infants was done. All patients received the same surfactant preparation (poractant-, 120 mg/1.5 mL) and the same dose (200 mg/kg), close monitoring of the infants will be mandatory. Results: There was no statistical significant difference between all groups as regard FiO2 before intervention while there was a high significant decrease in FiO2 at 6, 12 and 24 hours in thin tracheal catheter group, on the other hand, each group showed highly significant decrease in FiO over time after intervention also There was a statistical significant decrease in NCPAP and duration of O2 therapy in thin tracheal catheter group and There was no statistical significant difference between them as regard need for mechanical ventilation or occurrence of death during hospital stay. Conclusion: the endotracheal method is prior to the laryngeal mask method for surfactant alternative therapy.