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Aims Preventing stroke through endovascular treatment with vertebral artery stent remains a great challenge due to the occurrence of an in-stent restenosis. Materials & Methods In this study, a retrospective analysis was conducted in 90 patients who had been treated with VAS between 2004 and 2011 in Nanjing Drum Tower Hospital. Patients were followed up at 3 months, 6 months,and 1 year after VAS treatment and annually thereafter. For each time point, neurological function tests, vessel ultrasound and computer tomography angiography were performed to preliminarily screen the vessel stenosis. Digital subtraction angiography was used to verify the narrow sign on CTA or ultrasound. Clinical features of each patient including clopido-grel metabolization genes ( CYP2 C19, CYP3A4, and P2 Y12) were recorded with purpose to investigate the possible risk factors for the development of ISR. Results Single factor analysis dem-onstrated that hyperlipidemia ( P < 0.05) and CYP2 C19 ( P < 0.01) loss-of-function geno-type increased the likelihood of ISR. A multiple logistic cox regression analysis also showed that stroke patients with hyperlipidemia ( HR 3.719, 95% CI: 1.094-12.637, P = 0.035), and CYP2 C19 loss-of-function genotype ( HR 2.959, 95% CI: 1.325-6.610, P = 0.008) were more likely to suffer from ISR. Furthermore, CYP2 C19 alleles were mainly divided into three groups: wt/wt ( CYP2 C19 *1/*1), wt/m ( CYP2 C19 *1/*2 and *1/*3), and m/m ( CYP2 C19 *2/*2,*2/*3 and*3/*3). Recurrent rate of ischemic stroke in m/m and wt/m groups was higher than the wt/wt group ( OR: 0.141, 95% CI: 0.016-1.221, P = 0.042). Conclusion The study leads to the conclusion that hyperlipidemia and CYP2 C19 impotency are possible risk factors for the development of ISR in VAS-treated patients with ischemic. Moreover, VAS-treated patients with CYP2 C19 impotency were susceptible to recurrent stroke during our 54-month follow-up. [ABSTRACT FROM AUTHOR]