Object. Subdural hematoma (SDH) is a common diagnosis in neurosurgical and neurocritical practice. Comprehensive outcome data are lacking for nontraumatic SDH. The authors determined which factors are associated with in-hospital mortality in a large sample of patients with nontraumatic SDH.Methods. Using the Nationwide Inpatient Sample, the authors selected adults who had been hospitalized in the US between 2007 and 2009 and in whom a primary diagnosis of nontraumatic SDH (ICD-9-CM code 432.1) had been made. Demographics, comorbidities, surgical treatment, and discharge outcomes were identified. Univariate and multivariate analyses were performed to identify predictors of in-hospital mortality.Results. Among 14,093 patients with acute nontraumatic SDH, the mean age was 71.4 ± 14.8 (mean ± standard deviation). In addition, 22.2% of the patients were admitted during the weekend. Surgical evacuation was performed in 51.4% of the patients, and 11.8% of all patients died during hospitalization. In multivariate analyses, patient age (adjusted OR 1.02, 95% CI 1.012-1.022), congestive heart failure (adjusted OR 1.42, 95% CI 1.19-1.71), warfarin use (adjusted OR 1.41, 95% CI 1.17-1.70), coagulopathy (adjusted OR 2.14, 95% CI 1.75-2.61), mechanical ventilation (adjusted OR 16.85, 95% CI 14.29-19.86), and weekend admission (adjusted OR 1.19, 95% CI 1.02-1.38) were independent predictors of in-hospital mortality. Race (Hispanic: adjusted OR 0.65, 95% CI 0.51-0.83; black: adjusted OR 0.78, 95% CI 0.63-0.96), urban hospital location (adjusted OR 0.69, 95% CI 0.54-0.89), and surgical SDH evacuation (adjusted OR 0.52, 95% CI 0.45-0.60) were strong independent predictors for decreased mortality.Conclusions. One in 9 patients with nontraumatic SDH dies during hospitalization. Among the several predictors of in-hospital mortality, the weekend effect and treatment with surgical evacuation are potentially modifiable factors. Further investigation may lead to improvements in management and outcomes.