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High-frequency oscillatory ventilation (HFOV) is a type of mechanical ventilation with a protective potential characterized by a small tidal volume. Unfortunately, HFOV has limited monitoring of ventilation parameters and mechanical parameters of the respiratory system, which makes it difficult to adjust the continuous distension pressure (CDP) according to the individual patient’s airway status. Airway resistance <i>R</i>_aw is one of the important parameters describing the mechanics of the respiratory system. The aim of the presented study was to verify in vitro whether the resistance of the respiratory system <i>R</i>_rs can be reliably determined during HFOV to evaluate <i>R</i>_aw in pediatric and adult patients. An experiment was performed with a 3100B high-frequency oscillator, a physical model of the respiratory system, and a pressure and flow measurement system. The physical model with different combinations of resistance and compliance was ventilated during the experiment. The resistance <i>R</i>_rs was calculated from the impedance of the physical model, which was determined from the spectral density of the pressure at airway opening and the spectral cross-density of the gas flow and pressure at airway opening. <i>R</i>_rs of the model increased with an added resistor and did not change significantly with a change in compliance. The method is feasible for monitoring respiratory system resistance during HFOV and has the potential to optimize CDP settings during HFOV in clinical practice.