This study aimed to investigate the impact of controlling serum homocysteine on improving surgical outcomes in patients with moyamoya disease (MMD) and hyperhomocysteinemia. In this prospective observational cohort study, 477 patients with MMD post-encephaloduroarteriosynangiosis are divided into the HHcy-MMD post-control group (n = 193), HHcy-MMD uncontrolled group (n = 91), and MMD group (n = 193), with the HHcy-MMD post-control group further subdivided into good (homocysteine 0-10 μmol/L, n = 121) and general (homocysteine 10-15 μmol/L, n = 72) control groups. The differences in imaging and long-term clinical prognosis among the three groups were compared. No significant differences were noted in the Matsushima grade after encephaloduroarteriosynangiosis between the MMD group and HHcy-MMD post-control group (P >
0.05)
however, there was a significant difference between the HHcy-MMD post-control group and HHcy-MMD uncontrolled group (P <
0.001). A significant difference was noted between the good and general control groups in the Matsushima grade (P = 0.025) and long-term follow-up clinical outcomes (P = 0.035). The area under the curve of homocysteine levels for predicting adverse clinical outcomes was 85.48% (95% confidence interval: 80.31-90.65%). Effective control of serum Hcy level after EDAS surgery in Moyamoya disease patients with HHcy may lead to better prognosis.