Background: Nasal Continuous Positive Airway Pressure (NCPAP) has been the mainstay for non-invasive respiratory support for at risk neonates. Recent advances in High Flow Nasal Cannula (HFNC) usage including enhanced humidity and improved comfort factors have led to its widespread use, at times replacing NCPAP in many neonatal settings. Although ease of application cannot be matched by traditional CPAP devices, concerns about appropriate delivery of volume at a given pressure must be validated given that HFNC rarely exceeds 4 LPM. However, the NCPAP apparatus is often set at 8 LPM. Failures in both modalities have been described for reasons attributed to leak as well as inability to deliver an appropriate pressure or flow. Hypothesis: We asked if there were physical limitations imposed by flow delivery (or volume) that would result in differences in the success of HFNC and NCPAP. Materials and Methods: For this study, we created a model of 8 different sized patients with weights of 500 to 4000 grams. Simulated breathing patterns of 40 or 60 breaths per minute were assumed with nominal tidal volumes of 4 or 7 mL/kg/breath to a achieve a minute ventilation of 240 – 420 mL/kg/min. Spontaneous breathing inspiratory time (IT) was assumed to be fixed at 0.3 seconds. Available volume during IT was calculated and compared according to weight class for the breath epoch. Results: Even at the high flows, HFNC is not sufficient to meet the complete patient demand for volume as shown graphically. Discussion: HFNC flow is only available when the patient is actually taking a breath. There is no demand mode. As a result, in the best case situation, 70% of the liter flow is not delivered to the patient. If the instantaneous peak flow is exceeded at any time during the patient breathing cycle, additional flow must come from the environment in the form of a leak. Although peak flows were not demonstrated graphically in this particular model, documented peak inspiratory flows of as high as 6.7 LPM have been described in term infants (Pediatric Research (2009) 65, 352–356; doi:10.1203/PDR.0b013e318193f117). This flow may not be accommodated by HFNC if a leak of 50% is assumed even if HFNC is increased to as high as 8 LPM. Although NCPAP has often been described as more effective because of its ability to maintain pressure and avoid leak at the nasal interface, an 8 LPM “flow by” mechanism may be sufficient to support the high inspiratory peak flow demands in larger neonates. Conclusion: Although pressure and functional residual capacity maintenance through HFNC cannot be discounted, HFNC as used in the NICU may be insufficient to support the full inspiratory volume and flow demands of larger neonates.