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This study was aimed to evaluate the success rate of high-flow nasal cannula (HFNC) oxygen therapy and factors causing therapy failure. This prospective observational study included 131 children who received HFNC oxygen and followed-up in the pediatric emergency department, pediatric clinics, and pediatric intensive care unit between March 2018 and December 2019. The median age was 23.0 months (interquartile range [IQR]: 9.0–92.0) and 65 patients were male (49.6%). The most common reason for requiring HFNC oxygen therapy was pneumonia (n = 75, 57.3%). A complex chronic condition was present in 112 (85.5%) patients. Therapy success was achieved in 116 patients (88.5%). The reason for requiring treatment and the patients' complex chronic condition did not affect the success of the therapy (p = 0.294 and 0.091, respectively). In the first 24 hours of treatment, a significant improvement in pulse rate, respiratory rate, pH, and lactate level were observed in successful HFNC oxygen patients (p < 0.05). In addition, these patients showed a significant improvement in SpO2 and SpO2/FiO2 ratio, and a significant decrease in FiO2 and flow rate (p < 0.05). HFNC oxygen success rate was 95.6% in patients with SpO2/FiO2 ≥ 150 at the 24th hour; it was 58.0% in those with SpO2/FiO2 < 150 (p < 0.001). Caution should be exercised in terms of HFNC oxygen failure in patients with no significant improvement in vital signs and with SpO2/FiO2 < 150 during treatment.

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