The understanding of how pharyngeal pressure is transmitted to the trachea with high-flow nasal cannula (HFNC) implementation and the behavior of tracheal pressure in the presence of mouth leaks remains limited. This study aimed to assess the impact of HFNC administration on tracheal pressure by comparing measurements taken with open and closed mouth with varying flows. A crossover study was conducted between March 2019 and June 2023. Subjects age > 18 years, with a tracheostomy and who were in the process of decannulation were included. Tracheal and pharyngeal pressures were measured by using specific devices, with different HFNC flows and mouth conditions. Nine subjects were assessed: 77% women, with an average age of 60.5 years. Tracheal pressure was significantly higher than pharyngeal pressure only in baseline conditions (P = .03). With regard to the rest of the scenarios, there were no significant differences between both pressures. Tracheal pressure was higher than the baseline condition both with an open mouth and a closed mouth (P = .02). The tracheal pressure at 60 L/min with an open mouth was higher than at 40 L/min (P = .042). The median pharyngeal pressure with a closed mouth was higher than with an open mouth, both with 40 and 60 L/min of flow (P = .048 and P < .001, respectively). Pharyngeal pressure at 60 L/min with an open mouth was higher than both baseline condition and at 40 L/min (P = .002 and P = .043, respectively). However, pharyngeal pressure with the closed mouth was significantly higher than with the open mouth both with 40 and 60 L/min of flow (P = .031 and P = .02 respectively). The implementation of HFNC changes airway pressures with values that impact at a tracheal level as the flow used increases. Our data contribute to the difficult interpretation of the existing interrelation between the programmed flow and its effects on the respiratory system.