<i>Background:</i> We report the results of an open, randomized, multicenter trial that compared the efficacy of aspirin to oral anticoagulants (OA) for the prevention of vascular events in patients with symptomatic stenosis of the middle cerebral artery (MCA). <i>Methods:</i> Participants were randomly assigned to receive 300 mg/day of aspirin or a dose of OA (target INR 2–3). The MCA stenosis was demonstrated by conventional angiography or by at least two noninvasive examinations. Patients had either transient ischemic attack or cerebral infarct (CI) attributable to the MCA stenosis within 90 days before inclusion. The primary endpoint was: nonfatal CI, nonfatal acute myocardial infarct, vascular death and major hemorrhage. The patients were followed-up for a minimum of 1 year and a maximum of 3 years. <i>Results:</i> The study included 28 patients (14 in each treatment group); the average age was 67 ± 9.9 years. Men constituted 68% of the patients. After a mean follow-up of 23.1 ± 10.9 months, there were no recurrences of CI in both groups. No endpoint was reported in the aspirin group, but 2 patients in the OA group (14.3%) exhibited vascular events: 1 acute myocardial infarct and 1 intracerebral hemorrhage). However, this difference was not statistically significant (p = 0.48). <i>Conclusions:</i> Our study suggests that aspirin is the treatment of choice for the prevention of vascular events in patients with symptomatic MCA stenosis.