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We investigated the relationship between the neutrophil-lymphocyte ratio (NLR) and in-stent restenosis (ISR) in patients with femoropopliteal chronic total occlusions (CTOs). The study enrolled 180 patients who had undergone successful stenting treatment for femoropopliteal CTO. Patients with ISR were subsequently classified into 2 groups: early-ISR (within 1 year) and late-ISR (after 1 year). The clinical characteristics, angiographic data, and follow-up data were recorded. The baseline NLR was significantly higher in the early-ISR group than that in the non-ISR group [3.96(2.14) and 3.33(2.73), p = .04]. Receiver operating characteristic curve analysis suggested an optimum early ISR NLR cutoff point of 3.62, which showed a sensitivity and specificity of 73.4% and 80.4%, respectively (area under the curve: 0.707, 95% confidence interval: 0.603-0.792, P < .001). A subgroup analysis was performed based on the NLR value (<3.62 vs ≥3.62). In the NLR ≥3.62 subgroup, the incidence of early ISR was higher than that of late ISR (P < .01). In the multivariate analysis, NLR ≥3.62 was independently and positively associated with a higher risk of early ISR. In conclusion, NLR is independently associated with early ISR after stent implantation in patients with femoropopliteal CTO.