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Background and objective: Due to conflicting results in multiple studies, uncertainty remains regarding sex differences in incidence, pathophysiology, and outcome after intracerebral hemorrhage (ICH). We investigated the differential impact of sex on ICH severity and mortality.Methods: We analyzed prospectively collected ICH patients ascertained between 1994 and 2015 at a single tertiary care academic medical center. Clinical variables including past medical history, medications, hemorrhage characteristics, and case-fatality rate at 90 days and one year were assessed. Categorical and continuous characteristics were compared between sexes using chi-square test and t-test, respectively. Multivariable logistic regression was used to examine associations between sex and ICH severity as well as outcome.Results: A total of 2403 patients were investigated: 1292 (53.8 %) male and 1111 female (46.2%). Men with ICH were younger (72 vs. 77 years), had greater smoking and alcohol use, and were more likely to have hypertension, diabetes, hypercholesterolemia and coronary artery disease (all p< 0.05), consistent with previous studies. Lobar hemorrhages frequency was higher in women compared to men (46.5% lobar hemorrhages in women vs 37.1% lobar hemorrhages in men, p<0.001). Hematoma expansion was more frequent in men (19% vs. 12.5%, p=0.001) in univariate analysis, and after controlling for admission INR, time from onset to CT, baseline hematoma volume, spot sign and blood pressure values, men continued to demonstrate a higher risk of hematoma expansion (Odds Ratio [OR] 1.98, 95% confidence interval [CI] 1.11 - 3.52, p=0.020). The overall case fatality at 90 days was 37.4%. Controlling for univariate differences and known predictors of mortality, male sex was independently associated with both 90-day (OR 1.53, CI 1.05 - 2.23, p=0.025) and one year mortality (OR 1.80, CI 1.20 - 2.69, p=0.005).Conclusions: Sex independently affects early ICH expansion and outcome after ICH, with men experiencing a higher risk of both expansion as well as early and late mortality. Further research is needed to explore the biological mechanisms mediating these observed differences.