A ventilation system configured to provide respiratory support by intermittently delivering pressurized flow of breathable gas to a subject, the system comprising: a pressure generator configured to generate pressurized flow of breathable gas for delivery to an airway of the subject; an interface appliance in the form of a mouthpiece configured to be at least partially and releasably received into an airway orifice of the subject, the interface appliance further configured to deliver the pressurized flow of breathable gas generated by the pressure generator to the airway of the subject; one or more sensors configured to generate output signals conveying information indicating whether the subject has engaged with the interface appliance and is ready to receive pressurized flow of breathable gas through the interface appliance, wherein the one or more sensors are configured to provide an indication that the subject has received the interface appliance in his/her mouth and the one or more sensors are configured to provide an indication that the subject has made an inspiratory effort; and one or more processors configured to execute one or more computer program modules, the computer program modules comprising: a delivery triggering module configured to determine whether the subject has engaged with the interface appliance based on whether the subject has received the interface appliance in his/her mouth and configured to determine whether the subject is ready to receive the pressurized flow of breathable gas through the indication that the subject has made the inspiratory effort when there is movement of his/her mouth and/or tongue or when there is negative pressure at the interface appliance resulting from a diaphragmatic movement; and a control module configured to initiate and/or terminate delivery of the pressurized flow of breathable gas to the airway of the subject through the interface appliance based on a determination by the delivery triggering module as to whether the subject is ready to receive the pressurized flow of breathable gas, the control module further configured to control the pressure generator to adjust one or more parameters of the pressurized flow of breathable gas based on a prescribed therapy regimen designed to ventilate the subject. a pressure generator configured to generate pressurized flow of breathable gas for delivery to an airway of the subject; an interface appliance in the form of a mouthpiece configured to be at least partially and releasably received into an airway orifice of the subject, the interface appliance further configured to deliver the pressurized flow of breathable gas generated by the pressure generator to the airway of the subject; one or more sensors configured to generate output signals conveying information indicating whether the subject has engaged with the interface appliance and is ready to receive pressurized flow of breathable gas through the interface appliance, wherein the one or more sensors are configured to provide an indication that the subject has received the interface appliance in his/her mouth and the one or more sensors are configured to provide an indication that the subject has made an inspiratory effort; and one or more processors configured to execute one or more computer program modules, the computer program modules comprising: a delivery triggering module configured to determine whether the subject has engaged with the interface appliance based on whether the subject has received the interface appliance in his/her mouth and configured to determine whether the subject is ready to receive the pressurized flow of breathable gas through the indication that the subject has made the inspiratory effort when there is movement of his/her mouth and/or tongue or when there is negative pressure at the interface appliance resulting from a diaphragmatic movement; and a control module configured to initiate and/or terminate delivery of the pressurized flow of breathable gas to the airway of the subject through the interface appliance based on a determination by the delivery triggering module as to whether the subject is ready to receive the pressurized flow of breathable gas, the control module further configured to control the pressure generator to adjust one or more parameters of the pressurized flow of breathable gas based on a prescribed therapy regimen designed to ventilate the subject. a delivery triggering module configured to determine whether the subject has engaged with the interface appliance based on whether the subject has received the interface appliance in his/her mouth and configured to determine whether the subject is ready to receive the pressurized flow of breathable gas through the indication that the subject has made the inspiratory effort when there is movement of his/her mouth and/or tongue or when there is negative pressure at the interface appliance resulting from a diaphragmatic movement; and a control module configured to initiate and/or terminate delivery of the pressurized flow of breathable gas to the airway of the subject through the interface appliance based on a determination by the delivery triggering module as to whether the subject is ready to receive the pressurized flow of breathable gas, the control module further configured to control the pressure generator to adjust one or more parameters of the pressurized flow of breathable gas based on a prescribed therapy regimen designed to ventilate the subject.