The number of clinical research papers published worldwide on moyamoya disease (MMD) has increased recently. However, the majority of the literature comprises retrospective single-center studies collecting data on small numbers of patients. Several multi-center studies are ongoing in Japan; however, the current data are insufficient for comprehensively outlining the various characteristics of MMD. To enhance our knowledge on epidemiologic, vascular, and genetic aspects of MMD, a prospective multicenter registry will be established in Japan that will help to streamline clinical research as well as improve clinical treatments and long-term outcomes. Patients with MMD or secondary moyamoya syndrome referred to the participating centers will be invited to the registry. Demographic and physiological parameters, along with neuroimaging data will be collected chronologically. Clinical events, including neurological, medical, and surgical interventions will be recorded. Whole blood samples will be collected. Extra- and intra-cranial vascular tissue, and/or cerebrospinal fluid will also be collected from patients who undergo surgical revascularization. These biospecimens will be stored at the repositories and utilized for genome-wide association studies for identifying genetic variants, as well as tissue-specific proteomic, and/or molecular analyses. Ethics approval will be obtained at all facilities collecting biospecimens. The registry will provide descriptive statistics on functional outcomes, surgical techniques used, medications, and neurological events stratified according to patients’ clinical characteristics. We expect this study to provide novel insights in the management of MMD patients and design better therapies.