Background: The annual risk of stroke or cardiovascular events has been reported to be over 10% in middle cerebral artery stenosis. However, the prognosis of patients with middle cerebral artery occlusion (MCAO) remains unclear. We investigated the risk of cardiovascular events or death in patients with symptomatic or asymptomatic MCAO. Methods: Consecutive patients with MCAO demonstrated by transcranial Doppler sonography and magnetic resonance angiography were enrolled. Medical records were reviewed during the follow-up period and a telephone interview was conducted using a preformed questionnaire, comparing asymptomatic and symptomatic patients who had a history of ischemic stroke or transient ischemic attack in the same vascular territory. The composite outcome of ipsilateral stroke, hemorrhagic stroke, overall stroke, myocardial infarction (MI), any vascular death and nonvascular death was evaluated during the follow-up period. Results: Thirty-seven of the 48 patients were symptomatic and 11 were asymptomatic. During the mean follow-up period of 2.8 years, cardiovascular events or death occurred in a total of 13 patients: 1 from the asymptomatic group and 12 from the symptomatic group (overall stroke, 6; MI, 2; vascular death, 1; nonvascular death, 5). The annual rates of composite outcome (2.2 vs. 13.2%, p = 0.041) and overall stroke (0.0 vs. 6.6%, p = 0.048) were significantly lower in the asymptomatic group. Conclusion: These results suggest that the overall prognosis of MCAO is not worse than previously reported for patients with middle cerebral artery stenosis or internal carotid artery stenosis. Asymptomatic MCAO seems to be a benign condition associated with a low risk of subsequent stroke, MI or death under the optimal medical therapy.