Open studies suggest that treatment of obesity hypoventilation syndrome (OHS) by noninvasive ventilation (NIV) restores sleep quality and daytime vigilance and reduces cardiovascular morbidity. However, to our knowledge no randomized controlled trial (RCT) comparing NIV to conservative measures is available in the field. The goal of this study was to assess in patients with OHS, during an RCT, effects of 1-month NIV compared with lifestyle counseling on blood gas measurements, sleep quality, vigilance, and cardiovascular, metabolic, and inflammatory parameters.