To determine one-year clinical outcome of patients with first-ever acute ischemic stroke involving the territory of paramedian mesencephalic arteries (PMAS), we conducted a prospective study evaluating the cognitive functions of 28 patients with PMAS. Neuropsychological tests were performed during the first month of stroke onset and at the 12th month of follow-up. There were 12 women and 16 men. Mean age of onset for women and men was 70 years and 65 years, respectively. Progressing strokes occurred in 62% of patients and 96% developed a full-blown picture of the clinical triad of akinetic mutism, hypersomnolence, and bilateral blepharoptosis and ophthalmoparesis. Involuntary movements occurred in 6, and focal myoclonus in 4 patients. The top four associated risk factors were hypertension (68%), hyperlipidemia (57%), diabetes mellitus (46%), and atrial fibrillation (36%). Unilateral midbrain infarctions occurred in 12 patients and bilateral lesions in 16. Thalamic infarctions were unilateral in 10 and bilateral in 13 cases. Three of the 28 (11%) patients died of recurrent cerebral infarctions within 1 year of the onset of PMAS. The recurrent infarctions involved the basilar artery territory in two cases and the carotid system in another. One patient died of acute myocardial infarction. Of the 24 patients who had survived the stroke by 1 year, 20 (71%) developed dementia. We conclude that first-ever ischemic stroke with PMAS is not a benign syndrome. Most patients developed dementia by 1 year after the stroke.