Objective To explore the curative effects of pulmonary surfactant (PS) injected via venous indwelling needle instead of the endotracheal tube combined with continuous positive airway pressure(CPAP) in the treatment of premature infants with neonatal respiratory distress syndrome (NRDS).Methods 28 premature infants with NRDS were selected,12 cases with gestational age of 28-31 weeks,16 cases with gestational age of 32-34 weeks,and all the cases were treated with PS injected via venous indwelling needle combined with CPAP.The changes in clinical symptoms,blood gas analysis,oxygen saturation,and the parameters of CPAP after treatment were observed.The tracheal intubation in 72h,the second use of PS,respiratory support duration,hospital duration,and the complications between the MIST treatment group and INSURE treatment group were compared.Results There were significant differences in changes of clinical symptoms,percutaneous oxygen saturation,pH,partial pressure of oxyge,partial pressure of carbon dioxide,fraction of inspiration O2 and (positive end expiratory pressure) PEEP after treatment(all P ＜ 0.05).There were statistically significant differences in tracheal intubation in 72h,the second use of PS,complications and respiratory support duration between the MIST group and INSURE group (all P ＜ 0.05).There were no statistically significant differences in bronchopulmonary dysplasia,ROP,PDA,intracranial hemorrhage,and hospital duration (all P ＞ 0.05).Conclusion The therapy of PS injected via venous indwelling needle combined with CPAP in the treatment of premature infants is effective.The method MIST is simple and convenient,has less injury to premature infants,and can reduce frequency and dosage of the PS and respiratory support time.