A high frequency positive pressure ventilation system, the system comprising: an inspiratory subsystem to generate a pressurized flow of breathable gas for delivery to the airway of the subject; an expiratory flow generator configured to draw gas from the airway of a subject to a system outlet; one or more sensors configured to generate output signals conveying information related to one or more gas parameters at or near the airway of the subject; an exhalation valve configured to selectively control flow from the airway of the subject though the expiratory flow generator; one or more processors configured to execute computer program modules, the computer program modules comprising: a parameter module configured to determine a peak-to-peak pressure difference over a series of high frequency pressure cycles based on the output signals, and to determine a time averaged airway pressure level; a target module configured to obtain a target peak-to-peak pressure difference, and to obtain a target time averaged airway pressure level; and a control module configured to control the inspiratory subsystem, the expiratory flow generator and the exhalation valve to maintain the time averaged airway pressure level at the target time averaged airway pressure level over the series of high frequency pressure cycles, and to selectively control the inspiratory subsystem, the expiratory flow generator and the exhalation valve to maintain the peak-to-peak pressure difference at the target peak-to-peak pressure difference over the series of high frequency pressure cycles; wherein the parameter module is configured such that the peak-to-peak pressure difference is related to a difference between two or more consecutive maximum pressures. an inspiratory subsystem to generate a pressurized flow of breathable gas for delivery to the airway of the subject; an expiratory flow generator configured to draw gas from the airway of a subject to a system outlet; one or more sensors configured to generate output signals conveying information related to one or more gas parameters at or near the airway of the subject; an exhalation valve configured to selectively control flow from the airway of the subject though the expiratory flow generator; one or more processors configured to execute computer program modules, the computer program modules comprising: a parameter module configured to determine a peak-to-peak pressure difference over a series of high frequency pressure cycles based on the output signals, and to determine a time averaged airway pressure level; a target module configured to obtain a target peak-to-peak pressure difference, and to obtain a target time averaged airway pressure level; and a control module configured to control the inspiratory subsystem, the expiratory flow generator and the exhalation valve to maintain the time averaged airway pressure level at the target time averaged airway pressure level over the series of high frequency pressure cycles, and to selectively control the inspiratory subsystem, the expiratory flow generator and the exhalation valve to maintain the peak-to-peak pressure difference at the target peak-to-peak pressure difference over the series of high frequency pressure cycles; wherein the parameter module is configured such that the peak-to-peak pressure difference is related to a difference between two or more consecutive maximum pressures. a parameter module configured to determine a peak-to-peak pressure difference over a series of high frequency pressure cycles based on the output signals, and to determine a time averaged airway pressure level; a target module configured to obtain a target peak-to-peak pressure difference, and to obtain a target time averaged airway pressure level; and a control module configured to control the inspiratory subsystem, the expiratory flow generator and the exhalation valve to maintain the time averaged airway pressure level at the target time averaged airway pressure level over the series of high frequency pressure cycles, and to selectively control the inspiratory subsystem, the expiratory flow generator and the exhalation valve to maintain the peak-to-peak pressure difference at the target peak-to-peak pressure difference over the series of high frequency pressure cycles; wherein the parameter module is configured such that the peak-to-peak pressure difference is related to a difference between two or more consecutive maximum pressures.