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Because of the prevalence of extreme obesity in the United States, there has been an increase in prevalence of obesity hypoventilation syndrome (OHS). There is limited information on the characteristics and pattern of positive airway pressure (PAP) adherence in patients with OHS compared with eucapnic patients with obstructive sleep apnea (OSA). This article discusses in detail the impact of PAP therapy on outcomes in patients with OHS, compares adherence between continuous PAP and noninvasive ventilation in OHS, and compares PAP adherence in patients with OHS to patients with moderate to severe OSA enrolled in clinical trials designed to improve CPAP adherence.