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Positive airway pressure therapy is frequently used to treat obstructive sleep apnea in children. However, it is not known whether positive airway pressure therapy results in improvements in the neurobehavioral abnormalities associated with childhood sleep apnea. We hypothesized that positive airway pressure therapy would be associated with improvements in attention, sleepiness, behavior, and quality of life, and that changes would be associated with therapy adherence. Neurobehavioral assessments were performed at baseline and after 3 months of positive airway pressure therapy in a heterogeneous group of 52 children and adolescents. Adherence varied widely (mean use, 170 ± 145 [SD] minutes per night). Positive airway pressure therapy was associated with significant improvements in attention deficits (P < 0.001); sleepiness on the Epworth Sleepiness Scale (P < 0.001); behavior (P < 0.001); and caregiver- (P = 0.005) and child- (P < 0.001) reported quality of life. There was a significant correlation between the decrease in Epworth Sleepiness Scale at 3 months and adherence (r = 0.411; P = 0.006), but not between other behavioral outcomes and adherence. Behavioral factors also improved in the subset of children with developmental delays. These results indicate that, despite suboptimal adherence use, there was significant improvement in neurobehavioral function in children after 3 months of positive airway pressure therapy, even in developmentally delayed children. The implications for improved family, social, and school function are substantial. Clinical trial registered with www.clinicaltrials.gov (NCT 00458406).