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White matter (WM) is less vulnerable to ischemia than gray matter. In ischemic stroke caused by acute large-vessel occlusion, successful recanalization might therefore sometimes selectively salvage the WM, leading to infarct patterns confined to gray matter. This study examines occurrence, determinants, and clinical significance of such effects.Three hundred twenty-two patients with acute middle cerebral artery occlusion subjected to mechanical thrombectomy were included. Infarct patterns were categorized into WM− (sparing the WM) and WM+ (involving WM). National Institutes of Health Stroke Scale–based measures of neurological outcome, including National Institutes of Health Stroke Scale improvement or National Institutes of Health Stroke Scale worsening, good functional midterm outcome (day 90-modified Rankin Scale score of ≤2), the occurrence of malignant swelling, and in-hospital mortality were predefined outcome measures.WM− infarcts occurred in 118 of 322 patients and were associated with successful recanalization and better collateral grades (P<0.05). Shorter symptom-onset to recanalization times were also associated with WM− infarcts in univariate analysis, but not when adjusted for collateral grades. WM− infarcts were independently associated with good neurological outcome (adjusted odds ratio, 3.003; 95% confidence interval, 1.186–7.607; P=0.020) and good functional midterm outcome (adjusted odds ratio, 8.618; 95% confidence interval, 2.409–30.828; P=0.001) after correcting for potential confounders, including final infarct volume. Only 2.6% of WM− patients, but 20.5% of WM+ patients exhibited neurological worsening, and none versus 12.8% developed malignant swelling (P<0.001), contributing to lower mortality in this group (2.5% versus 10.3%; P=0.014).WM infarction commonly commences later than gray matter infarction after acute middle cerebral artery occlusion. Successful recanalization can therefore salvage completely the WM at risk in many patients even several hours after symptom onset. Preservation of the WM is associated with better neurological recovery, prevention of malignant swelling, and reduced mortality. This has important implications for neuroprotective strategies, and perfusion imaging-based patient selection, and provides a rationale for treating selected patients in extended time windows.