We conducted a randomized controlled pilot study in infants with critical bronchiolitis (n = 63) comparing high-flow nasal cannula (HFNC, n = 35) to continuous positive airway pressure (CPAP, n = 28). The primary outcome was treatment failure, defined as the need for bilevel positive pressure ventilation or endotracheal intubation. Treatment failure occurred in 10 patients (35.7%) in the CPAP group and 13 patients (37.1%) in the HFNC group (p = 0.88). Pediatric intensive care unit length of stay was similar between the CPAP and HFNC groups (5 [4–7] days and 5 [4–8] days, p = 0.46, respectively). In this pilot study, treatment with HFNC resulted in a rate of treatment failure similar to CPAP.