Noninvasive positive pressure ventilation (NPPV) is usually applied using pressure support ventilation (PSV). Proportional assist ventilation (PAV) is a newer mode that delivers assisted ventilation in proportion to patient effort. We hypothesized that PAV for NPPV would support gas exchange and avoid intubation as well as PSV and be more comfortable and tolerable for patients. Adult patients with acute respiratory insufficiency were randomized to receive NPPV with PAV delivered using the Respironics Vision ventilator or PSV using a Puritan-Bennett 7200ae critical care ventilator. Each mode was adjusted to relieve dyspnea and improve gas exchange until patients met weaning or intubation criteria, died, or refused to continue. Twenty-one and 23 patients were entered into the PAV and PSV groups, respectively, and had similar diagnoses and baseline characteristics, although pH was slightly lower in the PAV group (7.30 versus 7.35, p = 0.02). Mortality and intubation rates were similar, but refusal rate was lower, reduction in respiratory rate was more rapid, and there were fewer complications in the PAV group. We conclude that use of the PAV mode is feasible for noninvasive therapy of acute respiratory insufficiency. Compared with PSV delivered with the Puritan-Bennett 7200ae, PAV is associated with more rapid improvements in some physiologic variables and is better tolerated.