ObjectiveTo investigate the technical safety and outcome of in-stent restenosis (ISR) prevention with drug-eluting balloon (DEB) in patients with postirradiated carotid stenosis (PIRCS) undergoing percutaneous angioplasty and stenting (PTAS).MethodsBetween 2017 and 2021, we prospectively recruited patients with severe PIRCS for PTAS. They were randomly separated into two groups based on endovascular techniques performed with and without DEB. Preprocedural and early postprocedural (within 24 hours) MRI, short-term ultrasonography (6 months after PTAS), and long-term CT angiography (CTA)/MR angiography (MRA), 12 months after PTAS, were performed. Technical safety was evaluated based on periprocedural neurological complications and the number of recent embolic ischemic lesions (REIL) in the treated brain territory on diffusion-weighted imaging of early postprocedural MRI.ResultsSixty-six (30 with and 36 without DEB) subjects were enrolled, with one failure in techniques. For 65 patients in the DEB versus conventional groups, technical neurological symptoms within 1 month (1/29 (3.4%) vs 0/36; P=0.197) and REIL numbers within 24 hours (1.0±2.1 vs 1.3±1.5; P=0.592) after PTAS showed no differences. Peak systolic velocity (PSVs) on short-term ultrasonography was significantly higher in the conventional group (104.13±42.76 vs .81.95±31.35; P=0.023). The degree of in-stent stenosis (45.93±20.86 vs 26.58±8.75; P<0.001) was higher, and there were more subjects (n=8, 38.9% vs 1, 3.4%; P=0.029) with significant ISR (≥ 50%) in the conventional group than in the DEB group on long-term CTA/MRA.ConclusionsWe observed similar technical safety of carotid PTAS with and without DEBs. The number of cases of significant ISR were fewer and the degree of stenosis of ISR was less in primary DEB-PTAS of PIRCS than for conventional PTAS in the 12-month follow-up.