Background and Purpose— This study examines whether lesion shape documented on magnetic resonance diffusion-weighted imaging during acute stroke improves the prediction of the final infarct volume compared with lesion volume only. Methods— Diffusion-weighted imaging data and clinical information were retrospectively reviewed in 110 consecutive patients who underwent (n=67) or not (n=43) thrombolytic therapy for acute ischemic stroke. Three-dimensional shape analysis was performed on admission diffusion-weighted imaging data and 5 shape descriptors were developed. Final infarct volume was measured on T2-fluid-attenuated inversion recovery imaging data performed 30 days after stroke. Results— Shape analysis of acute ischemic lesion and more specifically the ratio of the bounding box volume to the lesion volume before thrombolytic treatment improved the prediction of the final infarct for patients undergoing thrombolysis ( R ² =0.86 in model with volume; R ² =0.98 in model with volume and shape). Conclusions— Our findings suggest that lesion shape contains important predictive information and reflects important environmental factors that might determine the progression of ischemia from the core.