Objective To compare the efficacy and safety of the non-invasive high frequency ventilation (NHFV) and non-invasive intermittent positive pressure ventilation (NIPPV)in neonates with respiratory distress syndrome (RDS) after extubation.Method Neonates with RDS from January 2015 to January 2016,who required high frequency ventilation after birth and were extubated after treatment were retrospectively studied.The enrolled patients were divided into NHFV group and NIPPV group to compare the rate of successful extubation within 7 days,non-invasive respiratory ventilation support time and complication incidence.Result In total 42 neonates were included,NHFV group were 21 cases and NIPPV group were 21 cases.The rates of successful extubation were not statistically different (71.4％ vs.80.9％,P ＞ 0.05);Compared with NIPPV group,NHFV group had shorter ventilation time [3.5 (2.2,4.1) d vs.4.6 (2.8,5.3)];the incidence of bronchopulmonary dysplasia,pneumothorax,intraventricular hemorrhage,periventricular leukomalacia,retinopathy of premature and necrotizing enterocolitis between groups were not statistically different (P ＞ 0.05).Conclusion NHFV is a new safe and efficient ventilation support method for extubated neonates,and needs further research.