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Background: Traumatic brain injury (TBI) and obstructive sleep apnea (OSA) are common in the general population and are associated with significant morbidity and mortality. The objective of this study was to assess hospital outcomes of patients with TBI with and without a pre-existing OSA diagnosis.Methods: We retrospectively analyzed data from the National Inpatient Sample (NIS) database of adult patients aged ≥ 18 years with a primary diagnosis of TBI. In-hospital outcomes were assessed among patients with TBI with and without pre-existing OSA hospitalized between 2005 to 2015 in the United States. Propensity score matching and conditional logistic regression models were used to analyze in-hospital mortality, length of hospitalization, and in-hospital complications among patients with TBI with and without a pretrauma OSA diagnosis.Results: In our TBI cohort, the overall prevalence of diagnosed OSA was 0.90%. Patients with OSA were mostly obese or morbidly obese older men with high comorbidity burden and sustained more severe head injuries yet were less likely to undergo craniotomy or craniectomy. Following propensity score matching, the odds risk (OR) of in-hospital mortality was significantly lower in the OSA group with TBI (OR 0.58; p < 0.001). Compared with the non-OSA group, patients with OSA had significantly higher risk of respiratory complications (OR 1.23) and acute heart failure (OR 1.25) and lower risk of acute myocardial infarction (OR 0.73), cardiogenic shock (OR 0.34), and packed red blood cell transfusions (OR 0.79). Patients with OSA spent on average 0.3 days less (7.4 vs. 7.7 days) hospitalized compared with the non-OSA group.Conclusions: Patients with TBI with underlying OSA diagnosis were older and had higher comorbidity burden; however, hospital mortality was lower. Pre-existing OSA may result in protective physiologic changes such as hypoxic-ischemic preconditioning especially to cardiac and neural tissues, which can provide protection following neurological trauma, which may lead to a reduction in mortality. [ABSTRACT FROM AUTHOR]