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Heated, humidified, high-flow nasal cannula oxygen therapy (HHHFNC) has been used to improve ventilation in preterm infants. There are no data on airway pressures generated and efficacy in bronchiolitis.The objective of this study was to determine nasopharyngeal (NP) pressures generated with HHHFNC therapy in bronchiolitis.We conducted a prospective, observational study to measure NP pressures at varying flow rates of HHHFNC therapy in moderate to severe bronchiolitis. Vital signs, bronchiolitis severity scores, and oxygen saturation were also noted.Twenty-five patients were enrolled (mean, 78.1 [SD, 30.9] days; weight, 5.3 [SD, 1.1] kg). Nasopharyngeal pressures increased linearly with flow rates up to 6 L/min. Beyond 6 L/min, pressure increase was linear but less accelerated. On average, NP pressure increased by 0.45 cm H2O for each 1-L/min increase in flow rate. There were significant differences between pressures in open- and closed-mouth states for flow rates up to 6 L/min. At 6 L/min, the pressure in open-mouth state was 2.47 cm H2O and that in closed-mouth state was 2.74 cm H2O (P < 0.001). Linear regression analysis revealed that only flow (not weight or gender) had an effect on generated pressure. Bronchiolitis severity scores improved significantly with HHHFNC therapy (pre: 14.5 [SD, 1.4], post: 10.4 [SD, 1.2]; P < 0.001).Increasing flow rates of HHHFNC therapy are associated with linear increases in NP pressures in bronchiolitis patients. Larger studies are needed to assess the clinical efficacy of HHHFNC therapy in bronchiolitis.