Background and Purpose -The progression of occlusive lesions in the major intracranial arteries was believed to be very rare in adult patients with moyamoya disease. The present study aims to clarify the incidence and clinical features of disease progression in adult moyamoya disease. Methods -For the past 15 years , 120 adult Japanese patients were diagnosed with moyamoya disease. Of these, 63 patients were enrolled in this historical prospective cohort study on a total o f 86 nonoperated hemispheres. All were followed up with a mean period of 73.6 mo nths. MRI and magnetic resonance angiography were repeated every 6 to 12 months, and cerebral angiography was performed when disease progression was suspected o n MRI and magnetic resonance angiography. Results -Disease progression occurred in 15 of 86 nonoperated hemispheres (17.4%per hemisphere) or in 15 of 63 patie nts (23.8%per patient) during the follow-up period. Occlusive arterial lesions progressed in both anterior and posterior circulations, in both symptomatic and asymptomatic patients, and in both bilateral and unilateral types. Eight of 15 patients developed ischemic or hemorrhagic events in relation to disease progres sion. Multivariate analysis revealed that the odds ratio conferred by a male pat ient was 0.20 (95%CI, 0.04 to 0.97). Conclusions -The incidence of disease pro gression in adult moyamoya disease is much higher than recognized before, and fe male patients may be at higher risk for it than male patients. Careful follow-u p would be essential to prevent additional stroke occurrence in medically treated adult patients with moyamoya disease, even if they are asymptomatic or are diagnosed as having unilateral moyamoya disease. Background and Purpose -The progression of occlusive lesions in the major intracranial arteries was believed to be very rare in adult patients with moyamoya disease. The present study aims to clarify the incidence and clinical features of disease progression in adult moyamoya disease. Methods-For the of these 63 prospective cohort studies on a total of 86 nonoperated hemispheres. Magnetic resonance angiography was repeated every 6 to 12 months, and cerebral angiography was performed when the disease progression was suspended on MRI and magnetic resonance angiography. Results-Dilation progression in 15 of 86 nonoperated hemispheres (17.4% per hemisphere) or in 15 of 63 patie nts (23.8% per patient) during the follow-up period. Occlusive arterial lesions progressed in both anterior and posterior Eight of 15 patients developed ischemic or hemorrhagic events in relation to disease progresion. Multivariate analysis revealed that the odds ratio conferred by a male patient was 0.20 (95 % CI, 0.04 to 0.97). Conclusions-The incidence of disease pro gression in adult moyamoya disease is much higher than recognized before, and fe male patients may be at higher risk for it than male patients. Careful follow-u p would be essential to prevent additional stroke occurrence in medically treated adult patients with moyamoya disease, even if they are asymptomatic or are diagnosed as having unilateral moyamoya disease.