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White matter hyperintensity (WMH) burden increases risk of ischemic stroke; furthermore, it predicts infarct growth in acute cerebral ischemia. We hypothesized that WMH would be less severe in patients with TIA as compared to those with acute ischemic stroke and completed infarct.Cases (TIA, n=30) and controls (acute ischemic stroke, n=120) were selected from an ongoing longitudinal cohort study of patients with stroke and matched for age, gender, and race/ethnicity. All subjects had brain MRI within 48 hours of presentation to evaluate for evidence of acute cerebral ischemia. WMH burden on MRI was quantified using a validated computer-assisted program with high inter-rater reliability.Median WMH volume in individuals with TIA was 3.7 cm3 (interquartile range, 1.5- 8.33 cm3) compared to 6.9 cm3 (interquartile range, 3.1–11.9 cm3) in acute ischemic stroke (P<0.04). In multivariable analysis, the odds of completed infarct were higher (OR, 2.19; 95% CI, 1.27–3.77; P<0.005) in subjects with larger volumes of WMH.WMH burden was significantly less in subjects with TIA as opposed to those with ischemic stroke. These data provide further evidence to support a detrimental role of WMH burden on the capacity of cerebral tissue to survive acute ischemia.