Air leaking through the mouth has been reported in kyphoscoliotic patients receiving nasal ventilation via volume-limited ventilators. This study accessed the frequency of occurrence and effect on sleep quality of air leaking through the mouth during nocturnal nasal ventilation in patients with chest wall and neuromuscular disease using pressure-limited ventilation. Overnight and daytime polysomnography was performed in six stable experienced users of nocturnal nasal noninvasive positive-pressure ventilation (NPPV) who had chronic respiratory failure due to neuromuscular disease or chest wall deformity. All patients used the BiPAP S/T-D ventilatory support system (Respironics, Inc., Murrysville, PA). Measures included sleep scoring, leak quantitation, diaphragm and submental electromyograms (EMGs), and tidal and leak volumes. All patients had air leaking through the mouth for the majority of sleep. Sleep quality was diminished because of poor sleep efficiency and reduced percentages of slow-wave and rapid eye movement (REM) sleep. Air leaking through the mouth was associated with frequent arousals during stages 1 and 2 and REM sleep that contributed to sleep fragmentation, but arousals were infrequent during slow-wave sleep. Despite prevalent leaking, oxygenation was well maintained in all but one patient. Patients used a-combination of passive and active mechanisms to control air leaking. Although nasal ventilation improves nocturnal hypoventilation and symptoms in patients with restrictive thoracic disorders, air leaking through the mouth is very common during use. The leaking is associated with frequent arousals during lighter stages of sleep that interfere with progression to deeper stages, compromising sleep quality. Portable pressure-limited ventilators compensate for leaks, maintaining ventilation and oxygenation, but further studies are needed to determine which interfaces and ventilator techniques best control air leaking and optimize sleep quality.