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Seizures after ischemic stroke have not been well-studied. We aim to determine the frequency, determinants, and significance of early seizures after thrombolysis for acute ischemic stroke.Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, multicenter, randomized controlled trial where patients with acute ischemic stroke were randomized to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) IV alteplase. The protocol prespecified prospective data collection on in-hospital seizures over 7 days postrandomization. Logistic regression models were used to determine variables associated with seizures and their significance on poor outcomes of death or disability (modified Rankin scale scores 3–6), symptomatic intracerebral hemorrhage (sICH), and European Quality of Life 5-Dimensions questionnaire [EQ-5D] over 90 days.Data were available for 3,139 acute ischemic stroke participants, of whom 42 (1.3%) had seizures at a median 22.7 hours after the onset of symptoms. Baseline variables associated with seizures were male sex (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.07–4.50), severe neurologic impairment (NIH Stroke Scale score ≥10; OR 2.16, 95% CI 1.06–4.40), and fever (OR 4.55, 95% CI 2.37–8.71). Seizures independently predicted poor recovery: death or major disability (OR 2.88, 95% CI 1.28–6.47), unfavorable ordinal shift of mRS scores (OR 1.94, 95% CI 1.10–3.39), and lower than median EQ-5D health utility index score (OR 3.50, 95% CI 1.37–8.91). There was no association of seizures with sICH in adjusted analysis.In thrombolysis-treated patients with acute ischemic stroke, seizures are uncommon, occur early, and predict poor recovery.NCT01422616.