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Background Measures of white matter hyperintensities (WMHs) represent a crucial part of post-stroke outcome prediction. Automatic WMH segmentation has proven particularly challenging in stroke cases. Using an improved method for WMH segmentation that incorporates stroke lesions, we set out to explore factors associated with higher WMH burden, as well as the association between WMH burden and post-stroke dependency across two different countries that may demonstrate significant variation in radiological presentation. Methods A total of 384 acute ischemic stroke (AIS) survivors from the Norwegian Cognitive Impairment After Stroke (Nor-COAST; NO) study and the Houston Methodist Registry of Neurological Endpoint Assessments among Patients with Ischemic and Hemorrhagic Stroke (REINAH; US) database were analyzed. MRI and clinical data were collected upon acute care hospital admission. WMHs were measured automatically using the nnU-Net methodology, taking into account the acute stroke lesion. Results No significant difference in WMH percentage was found between sites. Factors associated with higher WMH burden included only age in NO, while in US, very high age (≥ 85), smoking, and being underweight were key factors. The two sites showed significant differences in demographics and clinical characteristics: the US cohort exhibited greater racial heterogeneity, higher body mass index (BMI) with more extremely obese patients, higher National Institutes of Health Stroke Scale (NIHSS) scores, and more thrombectomies, whereas the NO cohort exhibited more tobacco use, hypercholesterolemia, and longer stay at the hospital. Post-stroke dependency was initially associated with higher WMH percentage overall but only remained significant after adjusment in Norwegians aged ≥85, while in the US, dependency was driven by stroke severity and treatment after adjustment. Conclusion Cohorts from the US and Norway exhibit no significant difference in WMH burden, but differ in the factors associated with WMHs.