ObjectiveThe risk of ischemic stroke with intracranial stenosis is associated with various serum lipid levels. However, the effects of changes in the lipid profile on the risk of in-stent restenosis have not been verified. Therefore, we investigated the association between the occurrence of in-stent restenosis at 12-month follow-up and changes in various lipid profiles.MethodsIn this retrospective cohort study, we included ischemic stroke patients who had undergone intracranial stenting for symptomatic intracranial stenosis between February 2010 and May 2020. We collected data about serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) levels, and calculated the TC/HDL-C and LDL-C/HDL-C ratios at baseline and after 12 months. We conducted multivariable logistic regression analyses to verify the association between various lipid profile changes and in-stent restenosis at 12 months.ResultsAmong the 100 patients included in the study (mean age, 60.8 ± 10.0 years; male: 80 [80.0%]), in-stent restenosis was found in 13 (13.0%) patients. The risk of in-stent restenosis of more than 50% was significantly decreased when TC/HDL-C ratio (odds ratio [OR] 0.22, [95% confidence interval (CI) 0.05–0.87]) and LDL-C/HDL-C ratio (OR 0.23, [95% CI 0.06–0.93]) decreased or when HDL-C levels (OR 0.10, [95% CI 0.02–0.63]) were increased at 12 months compared with baseline measurements.ConclusionsImprovement of HDL-C levels, TC/HDL-C ratio, and LDL-C/HDL-C ratio were associated with decreased risk of in-stent restenosis at 12-month follow-up. Management and careful monitoring of various lipid profiles including HDL-C levels, TC/HDL-C ratio, and LDL-C/HDL-C ratio may be important to prevent in-stent restenosis in patients with intracranial stenting.