We assessed the frequency, clinical and etiological correlates of acute supratentorial multiple infarcts from a hospital-based prospective stroke registry. Among 383 consecutive patients admitted with acute supratentorial infarcts, 352 had single infarcts and 31 (8.1 p. 100) had multiple infarcts on computed tomography. Multiple infarcts were bilateral in 18 patients and unilateral in 13 patients. In only one third of cases, could the diagnosis of multiple infarcts be suspected clinically before neuroimaging. Compared with patients with acute supratentorial single infarcts, the 18 patients with bilateral acute supratentorial multiple infarcts were younger and had a special etiological profile. Indeed, an unusual definite cause of stroke was identified in 8 of them, including coagulopathy/systemic disorders or rare non-atherosclerotic arteriopathy. Major cardiac sources of embolism were identified in 4, whereas large artery artherosclerosis accounted for only 2 cases. In 3 cases, uncertain causes (abnormalities whose link to stroke could not be clearly established) were found. The etiological workup was entirely negative in one. The 13 patients with unilateral acute supratentorial multiple infarcts did not differ significantly from those with acute supratentorial single infarct, concerning age, gender and risk factor profile. In 7 of them, the infarcts involved the anterior circulation (with or without associated posterior borderzone infarct). Six had ipsilateral ICA disease and one a major cardioembolic source associated with coagulopathy. In the other 6 patients, the infarcts involved the anterior and posterior circulations. Three had a major cardiac source of embolism and one a multifocal intracranial angiopathy. The cause of stroke was uncertain in one patient and the etiological workup was entirely negative in another. In conclusion, acute supratentorial multiple infarcts are not rare (8.1 p. 100). A minority of patients (32 p. 100) had a clinical picture suggesting multiple infarction. Some topographic patterns were associated with etiological correlates: unusual causes of stroke (coagulopathy/systemic disorders) and cardioembolism in bilateral acute supratentorial multiple infarcts; ipsilateral ICA disease in unilateral acute supratentorial multiple infarcts involving the anterior circulation (with or without associated posterior bordezone infarct): cardioembolism in unilateral supratentorial multiple infarcts involving the anterior and posterior circulations.