Objective: To determine whether high-flow nasal cannula oxygen (HFNCO) provided enhanced respiratory support in bronchiolitis than low-flow oxygen (LFO). Methods: We conducted a prospective, randomized controlled trial in children between 1-24 months diagnosed with moderate-to-severe bronchiolitis requiring oxygen therapy. Participants received LFO via face mask (6-10 L/min) or HFNCO (2 L*kg/min). Primary outcomes were the time that heart rate (HR) and respiratory rate (RR) return to their normal range for age and the time that baseline clinical respiratory score (CRS) regress to a lower severity score. Secondary outcomes were changes in HR, RR, and CRS over time, length of stay (LOS), duration of oxygen requirement, treatment failure, and adverse event (AE). Results: Eighty-seven children were enrolled (48 in LFO; 39 in HFNCO). The time that HR and RR baseline values reached their normal range for age was shorter in HFNCO therapy (2.0h [1.0-4.0] vs. 12.0h [2.0-24.0] and 4.0 h [2.0-12.0] vs. 24.0 h [4.0-48.0], respectively; P< .001); additionally, the improvement in CRS emerged more quickly in children treated with HFNCO (2.0 h [1.0-4.0] vs. 4.0 h [2.0-24.0]; P = .003). While the duration of oxygen requirement (19.0 h [4.0-30.0] vs. 29.5 h [14.0-45.7]; P = .009) and treatment failure (3% vs. 21%) was statistically lower in children who received HFNCO, there were no differences in LOS and AE between groups. Conclusion: HFNCO may provide enhanced respiratory support with a notable improvement in HR, RR, and CRS than LFO. Comprehensive studies are needed to assess the clinical efficacy of HFNCO therapy.