Objective To clarify the relationship of CYP2C19 gene polymorphisms with early in-stent restenosis one year after femoropopliteal artery stenting. Methods A total of 118 patients were enrolled, who firstly underwent femoropopliteal artery stenting in the Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University from March 2019 to March 2021.The patients orally took aspirin 100mg/d three days before operation and thereafter and clopidogrel 75mg/d from three days before operation to 1 year after operation. The distribution and expression of single nucleotide polymorphisms of clopidogrel metabolic active genes (CYP2C19*1, *2, *3, *17) were detected by polymerase chain reaction (PCR) fluorescence probe method. The patients were followed up by color Doppler ultrasound. The restenosis rate over 50% of a target vessel was defined as restenosis. SPSS statistics 22.0 was used for data analysis. According to different data type, one way ANOVA orχ² test was used for data comparison among groups. Results Among the 118 patients enrolled, 1 was of fast metabolic type (1/17, **17), 48 of normal metabolic type (1/1), 52 of moderate metabolic type (1/2, **3, **17, **17) and 17 of poor metabolic type (2/2, **3, **3). Restenosis occurred in 25.0% (12/48) of normal metabolic type, 19.2% (10/52) of moderate metabolic type and 53.0% (9/17) of poor metabolic type. χ² test showed significant difference in restenosis rate between poor metabolic type and normal metabolic type (P＜0.05) or moderate metabolic type (P＜0.05). Conclusion CYP2C19 gene polymorphism may be a risk factor for early restenosis after femoropopliteal artery stenting. The restenosis rate of poor metabolic type increases significantly compared with normal and moderate metabolic types.