OBJECTIVE To evaluate the efficacy of nasal mechanical ventilation in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure and to identify predictors of success or failure of nasal mechanical ventilation. METHODS Prospective case series. METHODS Medical intensive care unit in Veterans Administration Medical Center. METHODS Twelve chronic obstructive pulmonary disease patients treated during 14 episodes of hypercapnic respiratory failure. METHODS Nasal mechanical ventilation in addition to conventional therapy to treat hypercapnic respiratory failure. Patients underwent nasal mechanical ventilation for at least 30 mins, or longer if the therapy was tolerated. Responses to therapy and arterial blood gases were monitored. RESULTS Half of the episodes were successfully treated with nasal mechanical ventilation. There were no differences in age, prior pulmonary function, baseline arterial blood gases, admission arterial blood gases, or respiratory rate between those patients successfully treated and those patients who failed nasal mechanical ventilation. Unsuccessfully treated patients appeared to have a greater severity of illness than successfully treated patients, as indicated by a higher Acute Physiology and Chronic Health Evaluation II score (mean 21 +/- 4 [SD] vs. 15 +/- 4; p = .02). Unsuccessfully treated patients were edentulous, had pneumonia or excess secretions, and had pursed-lip breathing, factors that prevented adequate mouth seal and contributed to greater mouth leaks than in successfully treated patients (the mean volume of the mouth leak was 314 +/- 107 vs. 100 +/- 70 mL; p < .01). Successfully treated patients were able to adapt more rapidly to the nasal mask and ventilator, with greater and more rapid reduction in PaCO2, correction of pH, and reduction in respiratory rate. CONCLUSIONS Patients who failed nasal mechanical ventilation appeared to have a greater severity of illness; they were unable to minimize the amount of mouth leak (because of lack of teeth, secretions, or breathing pattern) and were unable to coordinate with the ventilator. These features may allow identification of poor candidates for nasal mechanical ventilation, avoiding unnecessary delays in endotracheal intubation and mechanical ventilation.