Objective: To evaluate airway pressure release ventilation as a partial ventilatory support mode by comparing a demand-flow airway pressure release ventilation system with synchronized intermittent mandatory ventilation and pressure support ventilation. Design: Prospective, nonrandomized, crossover trial. Setting: Medical intensive care unit in a university medical center. Patients: Sixteen consecutive patients without chronic obstructive pulmonary disease with mechanical ventilatory support of 25% to 75% of total minute ventilation on synchronized intermittent mandatory ventilation, or 25% to 75% of maximal pressure support level on pressure support ventilation. Interventions: Each mode of mechanical ventilation was supplied to patients with comparable levels of partial support for 30 mins. Measurements and Main Results: Among three different modes, demand-flow airway pressure release ventilation achieved the lowest peak airway pressure (airway pressure release ventilation 9.1 +/- 2.6 cm H2O; pressure support ventilation 18.4 +/- 4.6 cm H2O; synchronized intermittent mandatory ventilation 34.8 +/- 7.7 cm H2O; p <.001). Hemodynamic status and oxygenation status were similar among these three modes. Five (31%) of the 16 patients felt that demand flow airway pressure release ventilation was a less comfortable mode than synchronized intermittent mandatory ventilation or pressure support ventilation. This finding had no clear correlation with their duration of airway pressure release, preset machine deflation rate, or inspiratory/expiratory ratio of machine breath. Gross asynchrony of effort and ventilator cycling was noticed in two (13%) patients while they were receiving demand-flow airway pressure release ventilation. Conclusions: We conclude that for patients who do not have chronic obstructive pulmonary disease, demand-flow airway pressure release ventilation can provide effective partial ventilatory support with lower peak airway pressure when compared with pressure support ventilation and synchronized intermittent mandatory ventilation. However, this airway pressure release ventilation system may be less comfortable than the other two modes, and asynchrony may occur in some patients.