Abstract: Objective To observe the clinical effect of pulmonary surfactant (PS) combined with nasal continuous positive airway pressure (NCPAP) and pulmonary surfactant combined with nasal intermittent positive pressureventilation (NIPPV) in the treatment of neonatal respiratory distress syndrome (NRDS), so as to accumulate experience and provide reference for the optimization of NRDS treatment. Methods Total 122 children of NRDS in our hospital from July 2016 to December 2017 were selected and randomly divided into group PS combined with NCPAP and PS combined with NIPPV group, each group was treated with 61 cases, blood pH, arterial partial pressure of oxygen (PaO₂), positive end expiratory pressure (PEEP), partial pressure of carbon dioxide (PaCO₂), inhaled oxygen concentration (FiO₂), the incidence of complications, such as air leakage and nasal injury, were compared between the two groups, and the statistical analysis was carried out. Results Comparison of different stages in the group, there were significant differences on 24 h about the two groups after treatment with pH, PaO₂, PEEP, PaCO₂, FiO₂ before treatment (all P < 0.05). Comparing between the two groups, there were significant differences about p H, PaO₂, PEEP, PaCO₂, FiO₂ on 24 h, and the incidence of complications in the PS combined NIPPV group was lower than that in the PS combined NCPAP group. Conclusion PS combined with NIPPV and NCPAP can help to improve the arterial blood gas related indexes of children with NRDS, and can effectively reduce the incidence of complications. In comparison, the clinical efficacy of PS combined with NIPPV is more ideal.