Objective To investigate the association between arterial diameter discrepancy (ADD) and the incidence of in-stent stenosis (ISS) following flow diverter (FD) placement. Methods This retrospective analysis utilized data from a prospectively maintained multicenter registry across six advanced stroke centers in China. Patients who underwent FD treatment with the Pipeline Embolization Device (PED) or Tubridge Flow Diverter (TFD) between January 2020 and January 2024 were enrolled. Multivariable logistic regression models with progressive covariate adjustment and restricted cubic spline (RCS) analyses were used to evaluate the association between ADD and ISS at the 6-month angiographic follow-up. Sensitivity analyses assessed significant ISS as a secondary outcome. Subgroup analyses were performed to determine whether the association varied across patient characteristics. Results A total of 439 patients were included (53.5 ± 10.5) years. At the 6-month follow-up, the rates of complete aneurysm occlusion and ISS were 81.8% and 15.0%, respectively. Multivariable analysis revealed that each unit increase in ADD was associated with a 2.4-fold increase in the odds of ISS (OR = 2.42, 95% CI: 1.53 ~ 3.82, P < 0.001). These findings remained robust in sensitivity analyses. Subgroup analyses showed no significant effect modification across patient characteristics. RCS analysis demonstrated a threshold effect, with the risk of both ISS and significant ISS increasing markedly when ADD exceeded 0.30. Conclusions Higher arterial diameter discrepancy is independently associated with an increased risk of ISS following FD placement. These findings may aid neurointerventionalists in preprocedural risk stratification and device selection, highlighting the potential clinical value of tapered FDs for treating vessels with significant diameter mismatches.