BackgroundIliofemoral deep vein thrombosis (IFDVT) causes severe symptoms and affect the quality of life to a great extent. Endovascular thrombectomy and stent implantation have been a feasible strategie to alleviate the signs and symptoms of IFDVT. However, venous in‐stent restenosis (ISR) has become an emerging non‐negligible problem.MethodsTo evaluate the histological characteristics of venous ISR, neointima of arterial and venous ISR patients were collected and examed. To explore the effect of drug‐coated balloon (DCB) on venous ISR lesions, we conducted a single‐center retrospective case series study involving IFDVT patients with ISR after venous stenting who were treated with paclitaxel‐coated balloon dilatation.ResultsWe found a collagen‐rich matrix but not elastin, as well as fewer cells and less neovascularization in venous intimal hyperplasia compared with neointima in arteries. Thirteen IFDVT patients were involved in the study, with average preoperative stenosis degree of 87.69% ± 13.48%. After intervention, the stenosis degree was significantly reduced to 14.6% ± 14.36% immediately (p < 0.0001) and to 16.54% ± 15.73% during follow‐up (p < 0.0001). During follow‐up, the VEINES‐QOL scores (p < 0.0001), VEINES‐Sym scores (p < 0.0001), and Villalta scores (p = 0.04) of patients was improved significantly compared with those before intervention. No major adverse events were observed.ConclusionsThe use of DCB may have a positive effect in the treatment of venous ISR by targeting intimal hyperplasia. Moreover, the application of DCB dilatation in IFDVT stenting patients with ISR is deemed safe and effective.