Background Non-invasive ventilation combined with pulmonary surfactant (PS) therapy is recognised as a method for treating neonatal respiratory distress syndrome (NRDS). Among the administration, methods of PS, INtubation-SURfactant-Extubation (InSurE) and less invasive surfactant administration (LISA) have been widely discussed. LISA technique prevents patients from exposure to invasive positive pressure ventilation (PPV), thus improving the long-term outcomes of the respiratory system, but it faces challenges in resource-limited areas due to complexity and cost. The InSurE technique remains prevalent due to its simplicity. The new dual-lumen tracheal tube (NDT) is designed with a 0.2 mm diameter pathway on the sidewall for continuous administration of PS under continuous PPV. The purpose of this study is to compare the safety and effectiveness of the NDT InSurE technique versus the LISA technique in non-invasive ventilation for premature infants with NRDS, and to explore the applicability of the NDT. Background Non-invasive ventilation combined with pulmonary surfactant (PS) therapy is recognised as a method for treating neonatal respiratory distress syndrome (NRDS). Among the administration, methods of PS, INtubation-SURfactant-Extubation (InSurE) and less invasive surfactant administration (LISA) have been widely discussed. LISA technique prevents patients from exposure to invasive positive pressure ventilation (PPV), thus improving the long-term outcomes of the respiratory system, but it faces challenges in resource-limited areas due to complexity and cost. The InSurE technique remains prevalent due to its simplicity. The new dual-lumen tracheal tube (NDT) is designed with a 0.2 mm diameter pathway on the sidewall for continuous administration of PS under continuous PPV. The purpose of this study is to compare the safety and effectiveness of the NDT InSurE technique versus the LISA technique in non-invasive ventilation for premature infants with NRDS, and to explore the applicability of the NDT. Methods and analysis This is a multicentre randomised controlled trial, planned to recruit 132 premature infants who meet the inclusion criteria from January 2024 to December 2024. They will be randomly assigned to the InSurE group using the NDT (experimental group) and the LISA group. The study will be conducted in six tertiary neonatal intensive care units in Yunnan province. The primary outcome is the rate of mechanical ventilation within 72 hours after birth. Secondary outcomes include the procedure data and major complications of NRDS, also include respiratory infections within 12 months of corrected age. Discussion We assume that the NDT is not worse than the LISA catheter. Based on the characteristics of the NDT, continuous PPV during drug administration, we designed this study to compare the InSurE technique using the NDT with the LISA technique. We aim to explore more benefits of the NDT and confirm wider clinical applicability. It will provide more options for doctors when using the InSurE technique.