Abstract: There are no randomized controlled trials assessing the impact of noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) on cardiac function in obesity hypoventilation syndrome (OHS). Objective: To determine the efficacy of 2 months of NIV, CPAP or lifestyle modification (control) on echocardiographic changes. Method: OHS patients (n=302) were sequentially randomized by: 1) severe obstructive sleep apnea (OSA), into NIV, CPAP or control; 2) non-severe OSA, into NIV or control. ABG, spirometry, six-minute walk distance, Epworth sleepiness scale, polysomnography and transthoracic echocardiogram were evaluated. Results: We analyzed 2 groups: 1) with or without severe OSA and NIV or control treatments (entire OHS group; n=222); 2) with severe OSA and NIV, CPAP or control treatments (severe OSA subgroup; n=221). In the entire OHS group, NIV improved the left ventricular (LV) hypertrophy (mass index: -6.6 g/m2; 95%CI -11/-2.1 vs 3.6; 95%CI -1.1/8.3; adjusted p <0.035). In the severe OSA subgroup, only NIV improved the pulmonary artery pressure (PAP) (-3.4 mm Hg, 95%CI -5.3/-1.5; adjusted p=0.025 vs control and 0.033 vs CPAP). NIV decreased the LV hypertrophy compared with control (mass index: -5.7 g/m2; CI -11/4.4 vs 3.5; CI -1.5/8.6; adjusted p <0.015). Conclusion: Medium-term NIV therapy is more effective than CPAP and lifestyle modification in improving PAP and LV hypertrophy in OHS

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