SummaryObjectiveThe worldwide prevalence of obesity has reached epidemic proportions. Obesity hypoventilation syndrome (OHS) is a common yet largely undiagnosed and mistreated condition that likely carries a high mortality. The aim of this study was to determine the clinical characteristics, hospital outcome, outcome following hospital discharge and predictors of death in a large cohort of patients hospitalized with OHS. OHS is an important condition as many patients with this syndrome are misdiagnosed and receive inappropriate treatment.MethodsWe reviewed the electronic medical records of patients with unequivocal OHS admitted to a 525‐bed tertiary‐care teaching hospital over a 5‐year period. Demographic and clinical data as well as hospital disposition were recorded. In order to determine the patients' post‐discharge status, we linked our database to the database of death certificates of the State Registrar of Vital Records.ResultsWe identified 600 patients who met the inclusion criteria for this study. The patients' mean age was 58 ± 15 years with a mean body mass index of 48.2 ± 8.3 kg m−2; 64% were women. Thirty‐seven percent had a history of diabetes and 43% had been misdiagnosed as having chronic obstructive pulmonary disease, while none had been previously diagnosed with OHS. The most common admission diagnoses were respiratory failure, heart failure and sepsis. Ninety (15%) patients died during the index hospitalization. The patients' age, S‐creatinine, respiratory failure, sepsis and admission to the ICU were independent predictors of hospital mortality. The hospital survivors were followed for a mean of 1,174 ± 501 d (3.2 ± 1.3 years) from the index hospitalization. On follow‐up, 98 of the 510 (19%) hospital survivors died, with an overall cumulative mortality of 31.3%. The patients' age, S‐creatinine and admission to the ICU were independent predictors of post‐hospital mortality.ConclusionObesity hypoventilation syndrome is a common disease that is frequently misdiagnosed and mistreated and carries a 3‐year morality, which is significantly worse than that for most cancers combined. Considering the high mortality of this disease, all patients with a body mass index > 35 kg m−2 should be screened for OHS; those patients with both early and established OHS should be referred to a pulmonary and/or sleep specialist for evaluation for non‐invasive positive pressure ventilation, to a dietician for dietary counseling and lifestyle modification and to a bariatric surgeon for evaluation for bariatric surgery.