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Background: Among patients with a cardioembolic stroke, atrial fibrillation (AF) is a common comorbidity that is associated with a worse outcome. Mounting data indicates that AF may relate to stroke pathogenesis through mechanisms other than cerebral thromboembolic complications. We sought to identify different WMH patterns between patients with AF vs. non-AF related embolic ischemic strokes.Methods: We retrospectively analyzed consecutive patients with acute anterior circulation embolic ischemic stroke included in an academic medical center’s stroke registry. The stroke etiology was determined using the Causative Classification System of ischemic stroke. WMH lesion burden was assessed according to the Fazekas scale. An independent blinded examiner classified the different WMH-patterns, which included 5 categories: periventricular, subcortical spots, posterior subcortical patches, anterior subcortical patches, and severe confluent subcortical patches. Their association with AF was investigated using multivariable logistic regression (with backward elimination).Results: Overall, 174 patients (94 with and 80 without AF) were included. In unadjusted analyses, patients with AF had a significantly higher rate of anterior subcortical patches (p=0.018) and a lower rate of a periventricular pattern (p=0.022). After adjusting for WMH lesion burden, presence of multiple infarcts, infarct volume, the CHA2DS2-VASc score as well as pertinent two-way and three-way interactions the presence of anterior subcortical patches (OR 2.41, 95%-CI 1.02-5.72, p=0.045) and a higher CHA2DS2-VASc score (per point, OR 1.28, 95%-CI 1.08-1.52, p=0.005) were independently associated with AF.Conclusions: We found that AF is associated with specific WMH lesion patterns on MRI. The clinical significance of this observation remains to be clarified; yet it suggests that the well-established link between stroke and AF extends beyond thromboembolism and may reflect an underlying cardiovasculopathy that can be characterized by WMH. If confirmed in future studies further investigation into the underlying pathophysiological mechanisms may provide novel avenues to AF detection and treatment.