Abstract: Objective To observe the effect of continuous positive airway pressure ventilation combined with ambroxol in treatment of neonatal respiratory distress syndrome. Methods A total of 60 cases of neonatal respiratory distress syndrome were randomly divided into control group and observation group, with 30 cases in each group. All children were given vital signs monitoring, respiratory management, anti-infection and other basic treatments, the control group was given continuous positive airway pressure ventilation treatment, and the observation group was combined with ambroxol treatment on the basis of the control group. The total effective rate, oxygenation index(OI), duration of oxygenation and hospitalization condition were compared between the two groups. Results The total effective rate of clinical treatment in the observation group was significantly higher than that in the control group(96.67%vs. 73.33%, P<0.05); the OI in the observation group was significantly higher than that in the control group at 24 and 48 hours after treatment(P<0.05); the duration of oxygen therapy and hospital stay in the observation group were significantly shorter than those in the control group(P<0.05); the hospitalization expenses in the observation group were significantly lower than those in the control group(P<0.05). Conclusion Continuous positive airway pressure combined with ambroxol regimen has significant efficacy for neonatal children with respiratory distress syndrome.