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Stroke patients with large diffusion-weighted imaging (DWI) volumes are often excluded from reperfusion because of reckoned futility. In those with DWIvolume >70 mL, included in the THRACE trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke), we report the associations between baseline parameters and outcome.We examined 304 patients with anterior circulation stroke and pretreatment magnetic resonance imaging. Variables were extracted from the THRACE database, and DWI volumes were measured semiautomatically.Among 53 patients with DWIvolume >70 mL, 12 had favorable outcome (modified Rankin Scale score, ≤2) at 3 months; they had less coronary disease (0/12 versus 12/38; P=0.046) and less history of smoking (1/10 versus 12/31; P=0.013) than patients with modified Rankin Scale score >2. None of the 8 patients >75 years of age reached modified Rankin Scale score ≤2. Favorable outcome occurred in 12 of 37 M1-occluded patients but in 0 of 16 internal carotid-T/L–occluded patients (P=0.010). Favorable outcome was more frequent (6/13) when DWI lesion was limited to the superficial middle cerebral artery territory than when it extended to the deep middle cerebral artery territory (6/40; P=0.050).Stroke patients with DWI lesion >70 mL may benefit from reperfusion therapy, especially those with isolated M1 occlusion or ischemia restricted to the superficial middle cerebral artery territory. The benefit of treatment seems questionable for patients with carotid occlusion or lesion extending to the deep middle cerebral artery territory.