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Intravenous thrombolysis (ivT) with recombinant tissue plasminogen activator is established in acute ischaemic stroke. Little is known, however, about its efficacy in different stroke subtypes.A retrospective analysis of 128 733 patients from the Austrian Stroke Unit Registry was performed. Patients were classified as lacunar (LacS) or non-lacunar ischaemic stroke (nonLacS) by use of the clinical syndrome and technical findings. Outcome parameters were the short term improvement in the stroke unit [the difference of the National Institutes of Health Stroke Scale (NIHSS) score at admission and at discharge] and the modified Rankin Scale (mRS) score at 3 months. Patients were assigned to four groups according to thrombolysis and stroke subtype. To control for confounding, patients were matched for variables identified with impact outcome and for variables of general interest (NIHSS at admission, mRS before stroke and general risk factors).There were four matched groups of 401 cases each. In LacS median short term improvement was 3 [interquartile range (IQR) 2–5] NIHSS points in the thrombolysed patients and 2 (IQR 1–4) in the non-thrombolysed patients (P < 0.001). In the nonLacS groups median short term improvement was 3 (IQR 1–5) in the thrombolysed and 2 (IQR 0–4) in the non-thrombolysed patients (P < 0.001). At 3-month follow-up, ivT was significantly associated with a better functional outcome in LacS (P < 0.001) and nonLacS patients (P < 0.001). Taking magnetic resonance imaging as a requirement for stroke subtyping led to similar results.Patients with both lacunar and non-lacunar stroke benefitted from ivT. The degree of improvement was similar in both groups.