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OBJECTIVES The mechanisms of high-flow nasal cannula are still debated but may be mediated by the generation of low positive end-expiratory pressure and a washout of the airway dead space. The aims of this study were to assess the effects of high-flow nasal cannula on tidal volume using a noninvasive method using a time-of-flight camera, under various conditions. DESIGN A physiologic evaluation in healthy volunteers. SETTING An university hospital ICU. SUBJECTS Ten healthy volunteers were included in a physiologic study (CamOpt study, ClinicalTrials.gov identifier: NCT04096183). INTERVENTIONS All volunteers were submitted to 12 different conditions (i.e., gas flow [baseline = 0; 30-60 L/min]; mouth [open/closed]; respiratory rate [baseline; baseline + 10 breaths/min]). Tidal volume measurements were performed every minute, during a 6-minute recording period. In all combinations, reference respiratory rate was measured by using chronometric evaluation, over a 30-second period (RRREF), and by using the time-of-flight camera (RRTOF). MEASUREMENTS AND MAIN RESULTS Tidal volume increased while increasing gas flow whatever the respiratory rate and mouth condition (p < 0.001). Similar results were observed whatever the experimental conditions (p < 0.01), except one (baseline respiratory rate + 10 breaths/min and mouth closed). Tidal volume increased while decreasing respiratory rate (p < 0.001) and mouth closing (p < 0.05). Proportion of tidal volume greater than 10, 15, and 20 mL/kg changed while increasing the flow. RRTOF was in agreement with RRREF (intraclass correlation coefficient, 0.96), with a low mean bias (0.55 breaths/min) and acceptable deviation. CONCLUSIONS Time-of-flight enables to detect tidal volume changes under various conditions of high-flow nasal cannula application. Tidal volume increased significantly while increasing gas flow and mouth closing. Such technique might be useful to monitor the risk of patient self-inflicted lung injury or under assistance.