The present disclosure pertains to a high frequency positive pressure ventilation system. The system may be configured to maintain a time-averaged airway pressure level at a target time-averaged airway pressure level and/or a peak-to-peak pressure difference at a target peak-to-peak pressure difference. In some embodiments, the system is configured to control the inspiratory subsystem, the expiratory flow generator and exhalation valve in accordance with a high frequency positive pressure ventilation therapy regime.