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Background: The epileptogenicity of recombinant tissue-plasminogen activator (rt-PA) has been suggested, but seizures were not evaluated in randomised controlled trials., Objective: To evaluate whether rt-PA was associated with early seizures in a cohort of consecutive patients with cerebral ischaemia., Method: We included consecutive adults with ischaemic stroke due to large-vessel occlusion from the North-of-France stroke network selected for a mechanical thrombectomy (MT). Patients without contraindication received i.v. rt-PA. We evaluated stroke severity with the National Institutes of Health Stroke Scale (NIHSS), and functional status with the modified Rankin scale (mRS), and recorded epileptic seizures occurring between the end of imaging and day 7. We performed statistics using propensity analyses., Results: We included 1638 patients (783 men, 47.8%; median age 71 years; median NIHSS score 16; 1007 treated by rt-PA, 61.5%), in whom 60 (3.7%) developed early epileptic seizures. After adjustment on propensity scores, early seizures were associated with infections [adjusted odds ratio ( adj OR) 2.86; 95% confidence interval (CI) 1.37-5.95] and delay between stroke recognition and end of MT ( adj OR 1.04 for 10 min more; 95% CI 1.01-1.08), but not with rt-PA ( adj OR 1.35; 95% CI 0.55-3.33). The propensity-matched analysis of 343 pairs of patients found no difference in the occurrence of early seizures between those with and without rt-PA (p = 0.386)., Conclusion: We found no significant association between rt-PA and early epileptic seizures. If rt-PA has the potential for epileptogenicity, the magnitude of the effect should be modest compared to its favourable effect on functional outcome.