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High-flow nasal cannula (HFNC) therapy is a treatment for respiratory distress in neonates and children. In the present study, we assessed its effectiveness, comfort, and possible mechanism of action. Methods: We reviewed records of 46 patients treated with HFNC and estimated the modified COMFORT score (7 to 35 units), the respiratory clinical scale (0 to 12 units), and the oxygen saturation level. Data were collected at time 0 (before the use of high-flow), time 2 (60 to 90 min post-application), and at time 3 (8 to 12 hours post-application). Furthermore, we measured the nasopharyngeal pressure while on continuous positive air pressure (CPAP) as well as the differences in “lung expansion” demonstrated by the prestudy and post-study chest x-ray. Results: There were significant improvements in the modified COMFORT score (F1,45 = 40.03, P < .05), respiratory clinical scale (F1.69,76.15 = 121.19, P < .05), and oxygen saturation (F2,90 = 101.54, P < .05). Application of HFNC therapy created a significant average positive expiratory pressure of 4.0 ± 1.99 (SE) cm H2O. X-rays taken after initiation of HFNC showed either improved aeration of the lungs or no changes in 40 of 46 patients. Mechanical ventilation was needed in 5 of 46 patients. Conclusion: Our study indicates that high-flow nasal cannula improves the respiratory scale score, the oxygen saturation, and the patient's COMFORT scale. Its mechanism of action is application of mild positive airway pressure and lung volume recruitment.