BACKGROUND:De novo hypoxemic respiratory failure is defined as significant hypoxemia in the absence of chronic lung disease such as COPD, and excluding respiratory failure occurring in the immediate postoperative or postextubation period. We aimed to evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in patients with de novo hypoxemic respiratory failure. METHODS:We performed electronic database searches of PubMed, Cochrane Library, and Embase from inception to December 2018 to include randomized controlled trials that compared various oxygenation strategies in cases of de novo hypoxemic respiratory failure occurring in adult subjects without a preexisting chronic lung disease and excluding respiratory failure in the immediate postoperative or postextubation periods. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrI). RESULTS:16 studies were included, involving 2,180 subjects with a mean age of 61 ± 17 y (66% were male; 46% of the included subjects were treated with conventional oxygen, 27.8% were treated with NIV, and 25.8% were treated with HFNC). Compared to conventional oxygen, NIV was associated with reduced intubation rates (OR 0.42, 95% CrI 0.26-0.62) but no significant reduction in short-term (OR 0.73, 95% CrI 0.47-1.02) or long-term mortality (OR 0.60, 95% CrI 0.29-1.06). There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes. In a sensitivity analysis, the results remained consistent after exclusion of studies that included subjects with respiratory failure secondary to cardiogenic pulmonary edema. CONCLUSION:Among subjects with hypoxemic respiratory failure, NIV was associated with a significant reduction in intubation rates but not short- or long-term mortality when compared to conventional oxygen therapy. There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes.