BACKGROUND Hematoma expansion, the leading cause of neurologic deterioration after intracerebral hemorrhage (ICH), remains one of the few modifiable risk factors for poor outcome. In the present study, we explored whether common genetic variants within the hemostasis pathway were related to hematoma expansion during the acute period after ICH. METHODS Patients with spontaneous ICH who were admitted to the institutional Neuro-ICU between 2009 and 2011 were enrolled in the study, and clinical data were collected prospectively. Hematoma size was measured in patients admitted on or before postbleed day 2. Baseline models for hematoma growth were constructed using backwards stepwise logistic regression. Genotyping of single-nucleotide polymorphisms for 13 genes involved in hemostasis was performed, and the results were individually included in the above baseline models to test for independent association of hematoma expansion. RESULTS During the study period, 82 patients were enrolled in the study and had complete data. The mean age was 65.9 ± 14.9 years, and 38% were female. Only von Willebrand factor was associated with absolute and relative hematoma growth in univariate analysis (P < .001 and P = .007, respectively); von Willebrand factor genotype was independently predictive of relative hematoma growth but only approached significance for absolute hematoma growth (P = .002 and P = .097, respectively). CONCLUSIONS Our genomic analysis of various hemostatic factors identified von Willebrand factor as a potential predictor of hematoma expansion in patients with ICH. The identification of von Willebrand factor single-nucleotide polymorphisms may allow us to better identify patients who are at risk for hematoma enlargement and will benefit the most from treatment. The relationship of von Willebrand factor with regard to hematoma enlargement in a larger population warrants further study.