Moyamoya is a progressive cerebrovascular condition leading to stenosis of the internal carotid arteries (ICA) and formation of abnormal vasculature at the base of the brain. Patients ultimately suffer from ischemic and/or hemorrhagic stroke. In Kentucky, patients often present with comorbidities, which classifies them as having moyamoya syndrome (MMS). In this prospective observational study, we measured coagulable- and autoimmune-related factors in MMS subjects to identify possible therapeutic targets and help inform clinical care. Venous blood samples were collected from adult subjects diagnosed with MMS and analyzed by the UK Healthcare Clinical Laboratory. Blood samples, demographics, and medical records were obtained following written consent and enrollment between July 2020 and February 2024. Thirty-one subjects were enrolled (20 females and 11 males) with a median age of 45 years and 64.5% residing in an Appalachian county. The majority of the subjects were obese (BMI >30) and 29.0% had type 2 diabetes. Elevated factor VIII levels were detected in half the subjects, with speckled antinuclear antibody (ANA), and abnormal erythrocyte sedimentation rates (ESR) also detected in a large portion of the subjects. Elevated levels of factor VIII may put them at risk of developing thrombosis and increased ischemia, while the increased inflammatory state and possible undiagnosed autoimmune reactivity may play an important role in the progression of the condition. Evaluation of these factors in MMS patients can help to inform clinical care and provide targets for a treatment strategy.