BACKGROUND: Many patients who receive intravenous (i.v.) recombinant tissue-plasminogen activator (rt-PA) for acute cerebral ischemia were under angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) at stroke onset. ACE-Is and ARBs have neuroprotective properties in animal models. OBJECTIVE: To evaluate whether the 3-month outcome of patients treated with i.v. rt-PA for cerebral ischemia was influenced by on-going therapy with ACE-Is or ARBs. METHODS: This study was observational, conducted in two prospective registries of stroke patients treated with i.v. rt-PA. We evaluated outcomes with the modified Rankin scale and symptomatic intracranial hemorrhages (s-ICH) according to the ECASS2 criteria. We compared outcomes between patients with and without ACE-Is/ARBs according to the modified Rankin scale (mRS) at month 3, using logistic regression analyses adjusted on propensity scores, and propensity-matched analyses. RESULTS: Of 1803 patients, 455 (25.2%) were under ACE-Is (259), ARBs (188) or both (8). At 3 months, patients under ACE-Is or ARBs were more likely to have an mRS 0-1, but did not differ for mRS 0-2, s-ICH and death. After adjustment on propensity scores, the association between ACE-Is/ARBs and mRS 0-1 disappeared. The propensity-matched analysis, performed in 397 pairs of patients, found no difference in outcomes between patients with and without ACE-Is or ARBs. CONCLUSIONS: In patients treated by intravenous thrombolytic therapy for ischemic stroke, on-going treatment with ACE-Is or ARBs does not influence on outcomes after adjustment on baseline characteristics and propensity scores.