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Obesity can result in serious complications, including obesity hypoventilation syndrome (OHS). OHS patients may present with acute-on-chronic ventilatory failure, necessitating acute care management. The purpose of this review is to discuss the recent literature on acute ventilatory failure in OHS patients.Obese persons can develop acute hypercapnic respiratory failure and sleep hypoventilation due to disorders in lung mechanics, ventilatory drive, and neurohormonal and neuromodulators of breathing. Although there are no clearly defined predictors for OHS patients who are likely to develop acute hypercapnic respiratory failure, most such patients are middle-aged (mid-50s), morbidly obese, and have daytime hypercapnia, hypoxemia, and low serum pH values. Immediate ventilatory support, without sleep study confirmation, is necessary in most such patients. Patients with respiratory acidemia (pH <7.30) or altered mental status may require intensive care unit monitoring. Noninvasive application of bilevel positive airway pressure therapy is the recommended initial ventilatory support under close monitoring. Prompt initiation of noninvasive positive pressure ventilation reduces the need for invasive mechanical ventilation and rapidly improves the levels of blood gases.Obese patients with sleep hypoventilation have an increased risk of acute hypercapnic respiratory failure. Early diagnosis and implementation of noninvasive positive pressure ventilation is recommended for these patients.