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Background and purpose: Infarct topography has been suggested to predict functional outcome in ischemic stroke patients. However, little evidence could be found in regard to pretreatment imaging. We aimed to elucidate the impact of pretreatment infarct topography in predicting functional outcome in acute ischemic stroke.Methods: Our work is a sub-study of THRACE. 144 acute stroke patients assigned to receive intravenous thrombolysis plus mechanical thrombectomy were included. Infarct lesions were semi-automatically segmented on baseline diffusion weighted images. Regional lesion locations were decided according to automated anatomical labeling and JHU-WhiteMatter-labels atlases. A threshold was established in order to define, for each region, which percentage of infarction can predict poor clinical outcome (3 month-mRs 3-6) and then to define whether a region could be considered as infarcted. Finally, univariate and multivariate logistic analysis were performed.Results: In univariate analysis, basal ganglia, insula, inferior frontal and inferior parietal gyrus, temporal lobe, amygdala, internal capsule, corona radiata, superior longitudinal fasciculus, posterior thalamic radiation and uncinate fasciculus lesions were implicated in poor functional outcome in left-hemisphere stroke. Significant regions in right hemisphere were basal ganglia, temporal lobe, insula, amygdala, hippocampus and uncinate fasciculus. In multivariate analysis, eloquent regions for poor functional outcome were left internal capsule (OR=0.09), left inferior parietal gyrus (OR=0.03), right superior temporal gyrus (OR=0.09) and right amygdala (OR=0.03).Conclusion: Pretreatment infarct topography provides important prognostic value in functional outcome after acute ischemic stroke, and may optimize the individualized treatment decision-making.