Abstract Context Prader-Willi syndrome (PWS) is a rare, genetic, multisymptom, neurodevelopmental disease due to lack of the expression of the paternal genes in the q11 to q13 region of chromosome 15. The main characteristics of PWS are muscular hypotonia, hyperphagia, obesity, behavioral problems, cognitive disabilities, and endocrine deficiencies, including growth hormone (GH) deficiency. Sleep apnea and abnormal sleep patterns are common in PWS. GH treatment might theoretically have a negative impact on respiration. Objective Here we present the effect of GH treatment on polysomnographic measurements. Methods Thirty-seven adults, 15 men and 22 women, with confirmed PWS were randomly assigned to 1 year of GH treatment (n = 19) or placebo (n = 18) followed by 2 years of GH treatment to all. Polysomnographic measurements were performed every 6 months. A mixed-effect regression model was used for comparison over time in the subgroup that received GH for 3 years. Results At baseline median age was 29.5 years, body mass index 27.1, insulin-like growth factor 115 µg/L, apnea-hypopnea index (AHI) 1.4 (range, 0.0-13.9), and sleep efficiency (SE) 89.0% (range, 41.0%-99.0%). No differences in sleep or respiratory parameters were seen between GH- and placebo-treated patients. SE continuously improved throughout the study, also after adjustment for BMI, and the length of the longest apnea increased. AHI inconsistently increased within normal range. Conclusion SE improved during GH treatment and no clinical, significantly negative impact on respiration was seen. The etiology of breathing disorders is multifactorial and awareness of them should always be present in adults with PWS with or without GH treatment.