Objective: Severe acute bronchiolitis in infants is characterized by narrowing of the small airways and increased airway resistance, necessitating respiratory support and prolonged admission to PICU. Although a mixture of helium and oxygen gas (heliox) is known to decrease airway resistance, it is unclear whether heliox inhalation therapy shortens the length of PICU stay. This study aimed to determine whether respiratory support using heliox shortens the length of PICU stay and/or the duration of tracheal intubation. Methods: This prospective, interventional, single-center study included infants aged <2 years who were consecutively admitted to the PICU from November 2012 to December 2014 for treatment of severe acute bronchiolitis. Inclusion criteria were Modified Wood’s Clinical Asthma Score of ≥5 despite supportive therapy and arterial oxygen saturation of ≥92% in ≤40% oxygen. Patients on nasal continuous positive airway pressure received heliox through nasal prongs, whereas those on ventilators received heliox through tracheal tubes. The primary outcome was length of PICU stay and secondary outcomes were duration of tracheal intubation and safety of heliox inhalation therapy. Results: During the study period, 10 infants with severe acute bronchiolitis fulfilled the inclusion criteria (heliox group). Another 11 patients treated between April 2010 and March 2012 who were not eligible for heliox treatment were included as controls (control group). The length of PICU stay (4.7±1.1 days vs. 8.6±2.8 days, P<0.005) and the duration of tracheal intubation (3.8±1.4 days vs. 7.6±2.8 days, P<0.005) were shorter in the heliox group than in the control group, respectively. Conclusions: Heliox inhalation therapy during treatment for severe acute bronchiolitis may shorten the length of PICU stay and the duration of tracheal intubation.