This study sought to investigate subclinical changes in blood pressure in patients with Down syndrome prior to the acute presentation of patients with moyamoya syndrome (MMS) and compares this to patients with only Down syndrome (DS). 31 patients with MMS treated at Stanford University Hospital were retrospectively reviewed. Three blood pressure recordings from periods 6-12 months, 12-18 months, and 18-24 months, were obtained for each patient. These recordings were then compared against a retrospectively identified cohort of children with only DS. Statistical analysis was performed using generalized linear models with generalized estimating equations to account for blood pressures obtained at multiple time points. Median blood pressure percentiles in patients with MMS and DS from further to closer time-points were noted to be 33.5% (15-52) at 18-24 months, 42% (28-61) at 12-18 months, and 69.5% (39-73) at 6-12 months, compared to 29.3% (21-48.3) average in the DS only controls. There was no significant difference between the 18-24 month and 12-18 month periods (p=0.094), although there was a significant difference between the 6-12 month period and both the 12-18 month period and 18-24 month period (p<0.001). Adjusted for age and sex, the months from presentation were significantly reversely associated with increase of blood pressure percentile (p=0.001). This study identifies that subclinical elevations in blood pressure may predict development of MMD in patients with DS. Further prospective studies are needed to identify at risk patients with DS earlier to prevent irreversible neurologic injury.