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Background and purpose: Alteplase licensing approval in Europe does not advocate intravenous thrombolysis (IVT) for diabetic ischaemic stroke (IS) patients with previous cerebral infarction (PCI). Our aim was to assess whether concomitant diabetes mellitus (DM) and PCI are associated with symptomatic intracerebral haemorrhage (SICH) and poor outcome after IVT. Methods: Multicentre prospective registry, which included consecutive IVT-treated, acute IS patients from January 2003 to December 2010. The frequency of SICH (SITS-MOST criteria) and 3-month outcomes (mRS) were compared between the following groups: (i) diabetic patients with PCI (DM+/PCI+); (ii) diabetic patients without PCI (DM+/PCI−); (iii) non-diabetic patients with PCI (DM−/PCI+); and (iv) patients without diabetes or PCI (DM−/PCI−). Results: A total of 1475 patients were included. Thirty-four patients (2.3%) had known DM and PCI, 258 (17.5%) were diabetics without PCI, and 119 (8.1%) had a PCI and no DM. Thirty-six patients (2.6%) developed SICH, with no differences between groups ( P = 985). Fifteen (40.9%) DM+/PCI+ patients, 113 (46.5%) DM+/PCI− patients, 47 (42%) DM−/PCI+ patients and 414 (40.9%) DM−/PCI− patients had mRS ≥ 3 at 3 months ( P = 427). The presence neither of DM nor of PCI, nor their combination, had any impact on the risk of SICH or on outcome at 3 months after adjusting for age, stroke severity and glucose levels on admission. Conclusions: Acute IS diabetic patients with PCI who were treated with IVT had similar outcomes to patients without such history, with no increase in the rates of SICH. Thus, they should not be excluded from IVT only on the basis of DM and PCI. [ABSTRACT FROM AUTHOR]