Recent studies show that nasal high flow (NHF) therapy can support ventilation in patients with acute or chronic respiratory disorders. Clearance of dead space has been suggested as being the key mechanism of respiratory support with NHF therapy. The hypothesis of this study was that NHF in a dose-dependent manner can clear dead space of the upper airways from expired air and decrease rebreathing. The randomized crossover study involved 10 volunteers using scintigraphy with Krypton ( Kr) gas during a breath-holding maneuver with closed mouth and in 3 nasally breathing tracheotomized patients by volumetric capnography and oximetry through sampling CO and O in the trachea and measuring the inspired volume with inductance plethysmography following NHF rates of 15, 30, and 45 l/min. The scintigraphy revealed a decrease in Kr gas clearance half-time with an increase of NHF in the nasal cavities Pearson's correlation coefficient cc = -0.55, P < 0.01, the pharynx (cc = -0.41, P < 0.01), and the trachea (cc = -0.51, P < 0.01). Clearance rates in nasal cavities derived from time constants and MRI-measured volumes were 40.6 ± 12.3 (SD), 52.5 ± 17.7, and 72.9 ± 21.3 ml/s during NHF (15, 30, and 45 l/min, respectively). Measurement of inspired gases in the trachea showed an NHF-dependent decrease of inspired CO that correlated with an increase of inspired O (cc = -0.77, P < 0.05). NHF clears the upper airways of expired air, which reduces dead space by a decrease of rebreathing making ventilation more efficient. The dead space clearance is flow and time dependent, and it may extend below the soft palate. Clearance of expired air in upper airways by nasal high flow (NHF) can be extended below the soft palate and de facto causes a reduction of dead space. Using scintigraphy, the authors found a relationship between NHF, time, and clearance. Direct measurement of CO and O in the trachea confirmed a reduction of rebreathing, providing the actual data on inspired gases, and this can be used for the assessment of other forms of respiratory support.