Our aim was to compare the effects of nasal bilevel positive airway pressure (N-BiPAP) and nasal continuous positive airway pressure (N-CPAP) on gas exchange in preterm babies. Twenty preterm infants (mean gestational age, 26.3 weeks; mean weight at study, 1,033 g) were evaluated. Patients received two repeated cycles of N-CPAP alternated with N-BiPAP, for a total of four alternated phases, each phase lasting 1 hr. Transcutaneous PO2 (TcPO2), transcutaneous PCO2 (tcPCO2), pulsoximetry, and respiratory rate were recorded every 15 min. Arterial blood gases and acid-base balance were measured at the beginning of the first study period on baseline CPAP and at the end of the last study period on bilevel positive airway pressure. During the two N-BiPAP phases, a statistically significant (P < 0.001) increase of peripheral oxygen saturation and tcPO2, and a significant (P < 0.001) reduction of tcPCO2 and respiratory rate, were noted as compared to the two N-CPAP periods. In addition, a significant improvement of PO2 (P < 0.003) and a reduction of PCO2 were noted at the end of the test (P < 0.02). In conclusion, N-BiPAP, as compared to N-CPAP, improved gas exchange in preterm infants.