OBJECTIVE：To systematically evaluate the effects of phenytoin on 3 kinds of cardiovascular disease-related factors （Folic acid ，vitamin B 12 and homocysteine）in epilepsy patients ，and to provide evidence-based reference for clinical treatment of epilepsy. METHODS ：Retrieved from PubMed ，Google scholar ，CJFD，VIP and Wanfang database ，observational studies about using phenytoin （trial group ） versus using no antiepileptics （control group ） on the levels of folic acid ，vitamin B 12 and homocysteine in serum were collected during Jan. 1991-Jan. 2019. After data extraction of included literatures ，quality evaluation with evaluation criteria for cross-sectional study （AHRQ）scale，Rev Man 5.3 and Stata 11 softwares were used for statistical analysis. RESULTS ：A total of 10 studies were included ，involving 745 patients. Meta-analysis showed that the folic acid level of trial group was significantly lower than control group [SMD ＝－0.90，95％CI（－1.18，－0.62），P＜0.001]；the level of homocysteine in trial group was significantly higher than control group [SMD ＝1.22，95％CI（0.73，1.71），P＜0.001]. There was no significant difference in the levels of vitamin B 12 between 2 groups [SMD ＝－ 0.19，95％ CI（－ 0.39，0.02），P＞0.05]. CONCLUSIONS：Phenytoin can reduce the level of folic acid and increase the level of homocysteine in epilepsy patients.