In patients treated with noninvasive ventilation, sleep-related breathing changes can modify patient-ventilator interactions, which could reduce its effectiveness. The aim of this prospective observational study was to determine the impact of sleep/wake state on leaks, upper airway obstructive events, and asynchronies in patients treated by long-term noninvasive ventilation. Stable patients adapted to noninvasive ventilation were considered for nocturnal polysomnography. Unintentional leaks, upper airway obstructive events, and asynchronies were compared between sleep and awake periods. Twenty-eight patients were enrolled. Underlying diagnoses were neuromuscular disease (n = 11), chest wall disease (n = 8), and obesity-hypoventilation (n = 9). Leaks were more frequent in sleep than in awake periods, with a median of 10% (interquartile range [IQR], 0%-75%) vs 1% (IQR, 0%-9%) of time (P < .001), respectively. During sleep, asynchronies with and without associated leak affected 27% of breaths (IQR, 16%-39%) compared with non-leak-related asynchronies that were recorded in 8% (IQR, 3%-25%) of breaths (P < .001). Asynchronies affecting more than 10% of total breaths were more frequent in sleep (25 patients, 89%) than in awake time (8 patients, 29%; P = .25). Eleven patients (39%) presented with 5 or more upper airway obstructive events without reduction in ventilatory drive per hour of sleep. In patients adapted to home noninvasive ventilation, leaks, asynchronies, and upper airway obstructive events are frequent during the night and are concentrated in sleep periods. Asynchronies are often associated with leaks. These findings may have clinical implications considering that in patients with low sleep efficiency respiratory events could be underestimated if sleep is not evaluated. Martí S, Ferré A, Sampol G, etal. Sleep increases leaks and asynchronies during home noninvasive ventilation: a polysomnographic study. J Clin Sleep Med. 2022;18(1):225-233.