Objective: This study compared CO 2 clearance in a premature infant lung model connected to a high flow nasal cannula (HFNC) system supplied with oscillatory versus non-oscillatory flow.Design/Methods: The lung model was set to compliance 1.0 mL/cmH 2 O, RR 60 breaths/min, and 6 mL tidal volume. A 100% CO 2 was injected at a constant 15 mL/min.To create oscillation, HFNC flow was interrupted at rates of 4-6-8 and 10 Hz. equilibrated end-tidal CO 2 (ETCO 2 ) was recorded with and without oscillation at set flows of 2-8 L/min and repeated for each oscillation frequency.Results: Overall ETCO 2 decreased significantly (P < 0.001) during both non-oscillatory and oscillatory HFNC as set flow increased from 2 to 8 L/min by 26.3% and 60.8%, respectively. Oscillatory ETCO 2 levels decreased linearly compared to non-oscillatory HFNC with negligible difference at 2 L/min and a 48.4% difference at 8 L/min (P < 0.001). There were no differences in ETCO 2 levels between oscillation frequencies at any flow except at 6 Hz for which ETCO 2 was significantly lower (P < 0.01) than at 4, 8, and 10 Hz for 5-8 L/min HFNC flows. Amplitude of volume oscillations increased with increasing flow from 0.5 mL at 2 L/min to 4.0 mL at 8 L/min (P < 0.001), and decreased with increasing oscillation frequency.Conclusion: Oscillatory HFNC as compared to non-oscillatory was associated with significantly improved CO 2 clearance in this premature infant lung model. This simple modification of the HFNC system may prove to be a useful enhancement to this mode of non-invasive respiratory support for preterm infants at high risk for respiratory failure. K E Y W O R D S CO 2 clearance, HFNC, high frequency ventilation, non-invasive respiratory support, premature infants