Background: Obstructive sleep apnea (OSA) is present in almost 60% of patients with cerebrovascular disease and it is an independent predictor of ischemic stroke. Yet, the impact of OSA on outcomes of ischemic stroke is unclear. Some, small cohort studies indicate increased short-term mortality, whereas larger studies, with more complex logistic regression models, show decreased in-hospital mortality. Lower mortality could be attributed to chronic intermittent episodes of hypoxia affecting the remodeling of cerebral collateral circulation. We thought to investigate outcomes in a large unselected population of patients presenting with acute ischemic stroke. Methods: In a retrospective cohort study, using the 2014 Nationwide Inpatient Sample (NIS), we analyzed adult patients with acute ischemic stroke and OSA. We performed univariate analysis of age, sex, race, hospital location, hospital teaching status, insurance type, hospital bed size, Charlson Comorbidity Index and other relevant comorbidities and we included variables with p<0.2 in the multivariate logistic regression model. Results: A total of 95282 patients with acute ischemic stroke were identified. Patients with the associated diagnosis of OSA (5%) had a mean age of 66+/_0.2, vs 71+/_0.1, p<0.001 and a higher percentage of them were male (63% vs 48%, p<0.001). Patients with OSA were more likely to have hypertension (88% vs 83%, p<0.001), heart failure (24% vs 14%, p<0.001), chronic kidney disease (20% vs 14%, p<0.001) ESRD (3% vs 2%, p<0.001) and diabetes mellites (40% vs 30%, p<0.001). Patients with associated diagnosis of OSA had higher incidence of ventricular fibrillation and ventricular tachycardia (OR=1.27, 95%CI=1.02-1.58, p=0.27) with no difference in incidence of cardiac arrest (OR=1.14, 95%CI=0.78-1.66, p=0.50) and lower in-hospital mortality (OR=0.68, 95%CI =0.57-0.82, p<0.001). They were less likely to have hemiplegia (OR= 0.83, 95% CI=0.74-0.95, p=0.004) and less likely to receive a blood product transfusion (OR =0.71, 95%CI =0.54-0.93, p<0.014). There was no difference in utilization of percutaneous endoscopic gastrostomy (OR=0.90, 95%CI=75-1.07, p=0.23), incidence of shock (OR=1.13, 95% CI =0.66-1.90, p=0.66) and utilization of mechanical ventilation (OR=0.96, 95%CI =0.82-1.11, p=0.55) as well as in length of stay (Coef. =-0.039, 95% CI=-0.23—0.16, p=0.70) and total costs of hospitalization (Coef. =180.73, 95% CI= -1925-2287, p=0.87). Conclusion: Patients with OSA and ischemic stroke have a higher number of cardiovascular comorbidities. After adjustment with a complex multivariate regression model in a large population of patients, they have lower in-hospital mortality and lower incidence of hemiplegia. We also uncovered underdiagnosing of obstructive sleep apnea in National Inpatient Sample registry, which is a limitation of the study.