Background and purpose: Stenting appears to be a safe treatment for vertebral artery ostial stenosis (VAOS) with low complication rates and positive long-term effects. However, in-stent restenosis (ISR) after stenting is common. Drug-coated balloons (DCBs) are an effective management strategy for ISR in patients with coronary or carotid disease. In this study, we investigated the feasibility, safety, and effectiveness of DCB-assisted angioplasty for the treatment of ISR after treatment of VAOS. Research Design: The study included patients in the Department of Neurology at Beijing Tsinghua Changgung Hospital who underwent DCB-assisted angioplasty for ISR after previously undergoing stenting for VAOS. We retrospectively analyzed the clinical and functional outcomes in these patients. Results: Fourteen patients were enrolled in the study between January 2018 and April 2022. Five of the patients were female, and the mean age was 69.4 ± 7.5 years. The technical success rate was 100% and the mean operation time was 57.1 ± 29.2 minutes. No perioperative complications were reported. There were no new cases of cerebral infarction or transient ischemic attacks in hospital or during 6 months of follow-up. There were only 2 reports of ISR in the vertebral artery ostium in the 6 months following DCB-assisted angioplasty. The median modified Rankin scale score was 0. Conclusion: DCB-assisted angioplasty may be feasible for treatment of ISR after stenting of the vertebral artery ostium. However, more research is needed to confirm our findings.