Objective: To compare the applicability and effect of non-invasive ventilation (NIV) between acute ventilatory failure and oxygenation failure, and to describe variables that may be related with successful outcome of NIV in each type of respiratory failure. Design: Prospective clinical study in two distinct types of respiratory failure. Setting: Medical intensive care unit of a university-affiliated hospital. Patients: Twenty-six episodes of respiratory failure managed using NIV from a total of 106 episodes in 102 patients. Respiratory failure was defined as acute ventilatory failure (VF: PaCO2 ≥43 mmHg [5.7 kPa] with pH <7.35, n=19) or acute oxygenation failure (OF: PaO2/FiO2 <300 mmHg [40 kPa] with pH ≥7.35, n=87) necessitating mechanical ventilation. Interventions: The subjects were managed by NIV via face mask if they fulfilled the minimal requirement for NIV application. Respiratory pattern, arterial blood gases, complications and success rate of NIV were analysed in each group. Results: Eleven of 19 (57.9%) VF cases (M:F 7:4, 55.4±14.6 years) and 15 of 87 (17.2%) OF cases (M:F 12:3, 50.6±15.6 years) were suitable for a trial of NIV (p=0.017). Nine of 11 (81.8%) VF patients and six of 15 (40%) OF patients were successfully managed on NIV and were weaned from mechanical ventilation (p=0.051). In VF, NIV resulted in a significant reduction in respiratory rate at 12 hours (p=0.045), and significant improvements in PaCO2 and pH at 24 hours (p<0.05) compared to the baseline. In OF, the PaO2/FiO2 ratio improved significantly at 0.5 hour (p<0.05) in patients successfully managed with NIV. Conclusions: Non-invasive ventilation was more suitable for ventilatory failure than for oxygenation failure in terms of both applicability and success rate. For hypercapnic respiratory failure, a reduction in respiratory rate with NIV heralded the improvement in blood gases. NIV was less effective for hypoxaemic respiratory failure; an immediate (30-minute) improvement in PaO2/FiO2 ratio after its application was a predictor of success in this group.