Objective To detect the change in serum cystatin C (CysC) levels in very old male patients with vascular dementia (VaD) and to investigate its clinical significance. Methods A total of 45 male VaD patients with age over 75 years admitted in our department from January 2011 to December 2012 were enrolled in this study and assigned as observation group. Another 37 normal male persons at same age receiving physical examination during same period served as controls. Serum level of CysC in each patient was detected. Their skull CT scans or MR images were collected. The results were compared between the 2 groups. Results The serum level of CysC was markedly higher in the male VaD patients than in the normal controls [(1.98±0.64) vs (0.86±0.17)mg/L, P＜0.01]. There was negative correlation between Mini-Mental State Examination (MMSE) score and the serum level of CysC (r＝-0.592, P＜0.01). Conclusion The very old male VaD patients have significantly higher serum level of CysC, which might be a marker of vessel impairment, and be one of risk factors for VaD.