The aim of this study is to elucidate the efficiency and safety of Trimetazidine (TMZ) combined with oxiracetam in treating patients with Vascular Dementia (VD). From January 2013 to January 2015, 82 patients with VD were randomly assigned to a test and control group (41 cases each). In addition to the same basic medicine, oxiracetam was administered to the control group at a dose of 0.8 g, 3 times a day. Furthermore, in addition to the base treatment, TMZ was administered to the test group at a dose of 20.0 mg, 3 times a day for the 90-day treatment period. The cognitive function was measured before and after treatment by using the Mini-Mental State Examination Scale (MMSE), Clinical Dementia Rating Scale (CDR), and Barthel Index (BI) assessment while adverse reactions were also monitored. After treatment, the MMSE and BI scores (20.67 ± 4.01 and 80.29 ± 7.42, respectively) increased significantly in the test group compared with that of the control group (17.78 ± 3.55 and 71.04 ± 8.03, respectively). The CDR score (1.69 ± 0.35) decreased significantly in the test group compared with that in the control group (2.03 ± 0.27, P<0.01). Furthermore, obvious adverse reactions were not found in either group. The combined effect of TMZ and oxiracetam in the treatment of VD was better than that of the placebo and showed an excellent safety profile.