Background: Respiratory distress syndrome (RDS) is a primary cause of neonatal respiratory morbidity and mortality. For years, preterm infants with RDS have been managed with a combination of tracheal intubation and surfactant replacement therapy (SRT) followed by mechanical ventilation. SRT in preterm infants has been effective in decreasing infant morbidity and mortality and a major therapy in intubated preterm infants with respiratory distress after birth. Aim of the Work: To detect the efficiency of less invasive surfactant administration (LISA) and compare endotracheal catheter with intubation-surfactant-extubation (INSURE). Subjects and methods: Clinical trial. The current study was applied in the Neonatal Intensive Care Unit (NICU) in three hospitals in Dakahlia Governorate: Mit Ghamr General Hospital, Talkha General Hospital and Senbellawein General Hospital during the period from January to June 2019. Results: The results of this study suggest that thin tracheal catheter is the widely accepted route of surfactant replacement therapy and has slightly better outcome than the INSURE method. Future studies with a large number of patients are needed to show that this manner is as effective as thin tracheal catheter surfactant administration. Conclusion: The conclusion of the study is that thin tracheal catheter is the widely accepted route of surfactant replacement therapy, and has similar efficacy, feasibility and safety to its administration via endotracheal tube with higher success and less complications.