Abstract: Objective To compare the effects of nasal continuous positive airway pressure (NCPAP) and non-invasive neurally adjusted ventilatory assist (NIV-NAVA) on the stability of premature infants after extubation. Methods A total of 72 neonates who suffered from respiratory distress syndrome (RDS) and treated in Cangzhou Maternal and Child Healthcare Hospital from January 2019 to June 2020 were enrolled. According to the random table method, they were divided into two groups (n=36): a NCPAP group and a NIV-NAVA group. Their failure rate of weaning, the occurrence of asynchrony between man and machine, the index of man-machine asynchrony, total oxygen time, non-invasive time and non-invasive oxygen time after treatment were recorded. Meanwhile, blood gas analysis was performed before and after treatment to record pH value, partial pressure of carbon dioxide (PaCO₂), partial pressure of oxygen (PaO₂), and oxygenation index (OI). Furthermore, the occurrence of complications in different groups was recorded. Results There was no statistical difference in the failure rate of weaning, the occurrence of asynchrony between man and machine, the index of man-machine asynchrony, total oxygen time between the NCPAP group and NIV-NAVA group (P>0.05). The NIV-NAVA group require 2(1,3) days for noninvasive respiratory support, which was significantly shorter than 5 (3, 6) days in the NCPAP group (P<0.05). No statistical difference was found in pH, PaCO₂, and PaO₂ in the two groups before and after treatment (P>0.05). For patients in the NIV-NAVA group, the OI values were 238.52±32.94 and 258.18±40.75 for treatment of 12 h and 24 h, respectively, which were significantly higher than those in the NCPAP group (P<0.05). There was no statistical difference as to the incidence of complications between the NIV-NAVA group and the NCPAP group (P>0.05). Conclusions Compared with NCPAP, the application of NIV-NAVA after tracheal intubation and extubation in premature infants can shorten non-invasive respiratory support time, and reduce the occurrence of man-machine asynchrony, which is worthy of clinical use.