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Background: To date, an important aspect that has still not been clarified is the assessment of OHS severity. The purpose of this retrospective study was to evaluate whether grading OHS severity according to PaCO2 values may be useful in order to provide a more definite characterization and targeted management of patients. In this regard, baseline anthropometric and sleep polygraphic characteristics, treatment options, and follow up outcomes, were compared between OHS patients with different degree of severity (as assessed according to PaCO2 values). Methods: Patients were classified into three groups, according to PaCO2 values: 1) mild (46 mmHg ≤ PaCO2 ≤ 50 mmHg), moderate (51 mmHg ≤ PaCO2 ≤ 55 mmHg), severe (PaCO2 = 56 mmHg). Therefore, differences among the groups in terms of baseline anthropometric, and sleep polygraphic characteristics, treatment modalities and follow up outcomes were retrospectively evaluated. Results: Patients with more severe degree of hypercapnia were assessed to have increased BMI and bicarbonate levels, worse diurnal and nocturnal hypoxemia, and a more severe impairment in pulmonary mechanics compared to milder OHS. CPAP responders rate significantly decreased from mild to severe OHS. After follow up, daytime sleepiness (as measure by the ESS), PaO2, and PaCO2 significantly improved with PAP therapy in all three groups. Discussion and Conclusions: Classification of OHS severity according to PaCO2 levels may be useful to provide a more defined characterization and, consequently, a more targeted management of OHS patients. Further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]