Synchronized nasal intermittent positive pressure ventilation (SNIPPV) is non-invasive respiratory support that delivers ventilator breaths via the nasal prongs. We hypothesized that SNIPPV is more effective than nasal continuous positive airway pressure (NCPAP) in premature neonates due to decreased work of breathing (WOB). Fifteen infants (BW: 1,367 +/- 325 g, GA: 29.5 +/- 2.4 weeks) were studied on (a) NCPAP at 5 cmH(2)O (NCPAP5) and (b) three increasing SNIPPV settings achieved by NCPAP5 with additional delivered peak inspiratory pressures (PIP) of 10, 12, and 14 cmH(2)O. Tidal volumes and transpulmonary pressures were estimated via calibrated respiratory inductance plethysmography (RIP) and esophageal pressures, respectively. Inspiratory (WOB(insp)), resistive (RWOB), and elastic (WOB(E)) components of WOB were calculated using standard methods. Compared to NCPAP5, (a) WOB(insp) and RWOB were significantly lower with SNIPPV12, and were similarly lower with SNIPPV14 and (b) WOB(E) was significantly lower only with SNIPPV14. WOB components did not differ significantly for the three SNIPPV settings. Tidal volume, respiratory rate (RR), minute ventilation, compliance, and phase angle were similar for all four measurements. In conclusion, compared to NCPAP, the addition of ventilator-delivered PIP during SNIPPV decreases WOB in premature infants.