Background and Purpose— Poststroke cognitive decline and white matter lesions (WML) are related to poor poststroke survival. Whether cognitive reserve as reflected by educational history associates with cognitive decline, recurrent strokes, and poststroke mortality independent of WML is not known. Methods— A total of 486 consecutive acute mild/moderate ischemic stroke patients subjected to comprehensive neuropsychological assessment (n=409) and magnetic resonance imaging (n=395) 3 months poststroke were included in the study and followed-up for up to 12 years. Odds ratios (OR) for logistic and hazard ratios for Cox regression analyses are reported (OR and hazard ratio ≤1 indicates a beneficial effect). Results— Long educational history (per tertile) was associated with lower frequency of executive dysfunction in models adjusted for age, sex, marital status, and stroke severity (OR, 0.75; P <0.05) but not when adding WML as a covariate. In contrast, educational history was independently associated with less memory impairment (OR, 0.67; P <0.01), aphasia (OR, 0.69; P <0.05), visuospatial and constructive deficits (OR, 0.70; P <0.05), Mini-Mental State Examination score <25 (OR, 0.53; P <0.0001), and dementia (OR, 0.66; P <0.01). In Cox regression analysis, educational history was not associated with recurrent strokes, but it associated independently with favorable poststroke survival (hazard ratio, 0.86; P <0.05). Conclusions— Long educational history associates with less poststroke cognitive deficits, dementia, and favorable long-term survival independent of age, gender, marital status, stroke severity, and WML in patients with mild/moderate ischemic stroke. This supports the hypothesis that educational history as a proxy indicator of cognitive reserve protects against deficits induced by acute stroke.