Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to chronic respiratory insufficiency and failure. Use of home noninvasive ventilation (NIV) has been linked to improved outcomes including reduced mortality. Despite the importance of NIV, factors promoting optimal NIV usage and determinants of nonadherence have not been rigorously examined. Moreover, given that respiratory issues in DMD span between childhood and adulthood, examination across a broad age group is needed. The objectives of this study were to (1) evaluate NIV usage across a broad spectrum of patients with DMD, including both children and adults, and (2) identify biological and socioeconomic determinants of NIV usage and NIV nonadherence. We performed a retrospective review of all patients with DMD from February 2016 to February 2020 who underwent evaluation at associated pediatric and adult neuromuscular disease clinics. NIV use was determined objectively from device downloads. A priori, we defined nonadherence as < 4 hours use per night, quantified as the percentage of nights below this threshold across a 30-day period within 6 months of a clinic visit. We also assessed the average hours of NIV usage over this time period. Predictors examined included demographics, social determinants, and pulmonary function. 33 patients with DMD were identified, 29 (87%) of whom were using NIV (13 age < 21 years). Mean age was 22.9 ± 6.6 years (range 13-39 years), body mass index was 23.4 ± 10.4 kg/m2, and seated forced vital capacity was 23% ± 18% predicted. Mean nightly NIV usage was 7.4 ± 3.8 hours and mean percentage of nonadherent nights was 13% ± 30%. In univariable analysis, age did not predict use. Those with lower forced vital capacity had higher NIV usage hours (P = .01) and a trend toward less nonadherence (P = .06). Higher estimated household income demonstrated a trend toward increased usage hours and less nonadherence (both P = .08). Multivariable analysis found increased usage hours were predicted best by higher income, higher inspiratory positive airway pressure, and higher bicarbonate. Nonadherence was higher in those with lower income or higher forced vital capacity. In this cohort of adult and pediatric patients with DMD, most individuals were using NIV. While usage hours were higher with lower lung function, substantial variability remains unexplained by examined factors. Nonadherence was observed in some individuals, including those with advanced disease. Further investigations should focus on evaluating patient-oriented outcomes to define optimal NIV usage across the spectrum of disease and determine strategies to counteract issues with nonadherence. Hurvitz MS, Bhattacharjee R, Lesser DJ, Skalsky AJ, Orr JE. Determinants of usage and nonadherence to noninvasive ventilation in children and adults with Duchenne muscular dystrophy. J Clin Sleep Med. 2021;17(10):1973-1980.