Objective：To investigate the plasma homocysteine（Hcy） level in epilepsy patients with common antiepileptic drugs（AEDs） therapy and the intervention effect of multi-vitamin supplement therapy on high homocysteine（HHcy） and seizure status of patients with epilepsy. Methods：According to medication types，105 epileptic patients taking single AEDs were divided into carbamazepine group（CMZ group，n=25），valproate group（VPA group，n=23），phenytoin group（PHT group，n=30），topiramate group（TPM group，n=12），lamotrigine group（LTG group，n=15） and 30 healthy people were selected as healthy control group while 30 epileptic patients not taking AEDs as epileptic control group. The Hcy，folacin（Fol），vitamin B12（VitB12） levels were measured. Comparison on indicators was made among treatment group，healthy control group and epileptic control group. Thirty-two patients with HHcy were randomly se－lected for Fol and VitB12 replacement therapy and Hcy，Fol and VitB12 levels in patients among different time points before treat－ment，at 4 weeks after treatment and at 6 weeks after treatment were followed-up for 6 months and compared. Improvement be－tween patients with multi-vitamin supplement therapy and sin－gle AEDs therapy was compared. Results：Hcy levels were higher in CMZ group，PHT group，TPM group than in healthy control group and epileptic control group（FHcy=31.581，P<0.001）. There were 2 cases of HHcy in epileptic control group，VPA group and LTG group respectively，accounting for 6.67%，8.70% and 13.33% respective－ly，without differences（P<0.05）. There were 20 cases（80.00%） of HHcy in CMZ group，20 cases（66.67%） in PHT group and 8 cases（66.67%） in TPM group，higher than those in epileptic control group（χ2=30.556，P=0.000）. There were differences in Hcy，Fol and VitB12 levels of 30 HHcy patients taking vitamin intervention treatment at different time points after the treatment（FHcy=482.541，P=0.000；FFol=48.123，P=0.000；FVitB12=26.286，P=0.000）；Hcy levels were decreased and Fol and VitB12 levels were increased after the treatment. Among 30 HHcy patients receiving vitamin intervention，12 patients completely controlled seizures，13 patients improved markedly，three patients were effective，with total effective rate of 93.33%；one patient was invalid and one patient was deteriorated. Among 22 patients only took AEDs treatment，seven patients completely controlled seizures，nine patients improved markedly，three cases were effective with total efficiency of 84.34%；two patients ineffective and one patient was deteriorated，with statistically signifi－cant difference（Z=-4.426，P<0.01）. Conclusions：Taking AEDs can cause HHcy while vitamin supplement therapy can be effective in reducing Hcy levels in patients with epilepsy and number of patients with seizures.