Early in-stent restenosis after stent-protected angioplasty of the carotid artery (SPAC) is an infrequent, but potentially harmful condition for patients with carotid artery disease. METHODS In our retrospective single-center analysis of 176 patients with carotid artery stenting between 2009 and 2015, using duplex ultrasound, we detected 9 patients with high-grade carotid artery in-stent restenosis. All restenosis patients were treated with a drug-eluting balloon (DEB) to prevent recurrent neointimal hyperplasia. One patient had bilateral carotid artery disease with bilateral in-stent restenosis, and 1 patient needed repeated DEB treatment 19~months after the first DEB intervention, so 11 DEB procedures, in total, were performed. RESULTS The median time-interval between primary carotid artery stenting and first DEB-treatment was 9~months. In 3 of the 11 interventions, the DEB treatment was assisted by an additional stent. One repeat DEB treatment was necessary, and three DEB treatments were followed by a secondary stent. No peri-interventional complications (TIA, stroke, or death) were observed during or after DEB intervention. Therefore, in the entire group, the 1y event-free survival (EFS) was 100%, and the 2y/3y/5y EFS was 83%. CONCLUSION DEB intervention seems to be an effective and safe treatment for patients with high-grade in-stent restenosis after SPAC.