OBJECTIVE To compare the clinical effects of nasal intermittent positive pressure ventilation (NIPPV) and nasal continuous positive airway pressure (NCPAP) in the treatment of neonatal respiratory distress syndrome. METHODS A prospective, randomized, controlled, single-center study was performed on 67 premature infants with NRDS between March 2011 and May 2012 and selected according to the inclusion and exclusion criteria. These premature infants were randomly assigned to receive NIPPV and NCPAP. Oxygenation index (OI), pH, PaCO2, duration of respiratory support, complications, success rate, hospital mortality, and incidence of bronchopulmonary dysplasia (BPD) were compared between the two groups. RESULTS Sixty-two patients were finally enrolled in the study, including 32 cases in the NIPPV group and 30 cases in the NCPAP group. After one hour of non-invasive ventilation, OI in the NIPPV group was higher than the NCPAP group (P<0.05), but there were no significant differences in pH and PaCO2 between the two groups (P>0.05 for both). A significantly lower proportion of infants needed mechanical ventilation via endotracheal tube (MVET) when they were treated initially with NIPPV than when they were treated initially with NCPAP (P<0.05). The NIPPV group had a significant higher success rate than the NCPAP group (P<0.05), but there was no significant difference in duration of respiratory support between the two groups (P>0.05). In addition, no significant differences in incidence of pneumothorax, hospital mortality and incidence of BPD were seen between the two groups (P>0.05 for all). CONCLUSIONS Compared with NCPAP, NIPPV can significantly decrease the proportion of premature infants with NRDS in need of MVET. However, there is no evidence that NIPPV can significantly reduce hospital mortality and incidence of BPD in premature infants with NRDS.