Obesity hypoventilation syndrome (OHS) is a disease defined by the combination of obesity, sleep disordered breathing, and daytime hypercapnia during wakefulness, in the absence of an alternative neuromuscular, mechanical, or metabolic explanation for hypoventilation. This disease is largely underrecognized and often discovered when acute respiratory failure occurs. Several studies have reported that OHS is associated with multiple systemic complications, including heart failure; obesity is both a risk factor for and a direct cause of heart failure (HF) and is associated with a variety of adverse hemodynamic changes that predispose to cardiac remodeling and ventricular dysfunction. In obese patients, total blood volume and cardiac output correlate positively and proportionately with the degree of body weight. The increase in cardiac output and cardiac work are attributable to a rise in left ventricular stroke volume and stroke work. Mechanical ventilation may reduce morbidity and mortality, resulting from respiratory functioning variations, but it has less impact on cardiovascular outcomes. The effect of BPAP-AVAPS was greater than that of CPAP and AVAPS had the best effect in reducing PaCO2. The effect of BiPAP-AVAPS was greater than what CPAP and AVAPS had in reducing PaCO2. In this chapter, we review the best-available evidence in international literature about the association between obesity hypoventilation syndrome (OHS), heart failure and their treatment with mechanical ventilation.