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Tracheal intubation of ICU patients is frequently associated with severe hypoxemia. Although noninvasive ventilation reduces desaturation during intubation of severely hypoxemic patients, it does not allow for per-procedure oxygenation and has not been evaluated in mild-to-moderate hypoxemic patients for whom high-flow nasal cannula oxygen may be an alternative. We sought to compare pre- and per-procedure oxygenation with either a nonrebreathing bag reservoir facemask or a high-flow nasal cannula oxygen during tracheal intubation of ICU patients.Prospective quasi-experimental before-after study (ClinicalTrials.gov: NCT01699880).University hospital medico-surgical ICU.All adult patients requiring tracheal intubation in the ICU were eligible.In the control (before) period, preoxygenation was performed with a nonrebreathing bag reservoir facemask and in the change of practice (after) period, with high-flow nasal cannula oxygen.Primary outcome was median lowest SpO2 during intubation, and secondary outcomes were SpO2 after preoxygenation and number of patients with saturation less than 80%. One hundred one patients were included. Median lowest SpO2 during intubation were 94% (83–98.5) with the nonrebreathing bag reservoir facemask versus 100% (95–100) with high-flow nasal cannula oxygen (p < 0.0001). SpO2 values at the end of preoxygenation were higher with high-flow nasal cannula oxygen than with nonrebreathing bag reservoir facemask and were correlated with the lowest SpO2 reached during the intubation procedure (r = 0.38, p < 0.0001). Patients in the nonrebreathing bag reservoir facemask group experienced more episodes of severe hypoxemia (2% vs 14%, p = 0.03). In the multivariate analysis, preoxygenation with high-flow nasal cannula oxygen was an independent protective factor of the occurrence of severe hypoxemia (odds ratio, 0.146; 95% CI, 0.01–0.90; p = 0.037).High-flow nasal cannula oxygen significantly improved preoxygenation and reduced prevalence of severe hypoxemia compared with nonrebreathing bag reservoir facemask. Its use could improve patient safety during intubation.