Purpose Intracranial atherosclerosis disease (ICAD) is an essential cause of stroke. The characteristics of effective treatment include low periprocedural risk and a sustained treatment effect. Angioplasty with a conventional balloon for ICAD is safe but has a dauntingly high restenosis rate. Drug-coated balloon (DCB) angioplasty might reduce the risk of restenosis while maintaining the overall safety of the procedure. Methods This study included symptomatic ICAD patients with more than 70% stenosis. Intermediate catheters were placed distally, and the lesions were predilated with a conventional balloon, followed by a DCB (SeQuent Please, B Braun, Melsungen, Germany). The primary endpoint was any stroke or death within 30 days or ipsilateral ischemic stroke thereafter. The secondary endpoint was arterial restenosis of more than 50% during follow-up. Results A total of 39 sessions of DCB angioplasty were performed for 39 lesions in 35 patients between October 2015 and April 2018 in a single center. All of the DCBs could be navigated to the lesions. Major periprocedural complications were noted in two patients (5.7%, 2/35), and minor periprocedural complications were also noted in two patients (5.7%, 2/35). The average percentages of stenosis of the lesions were 76.6%& x202f;+/- 7% before treatment, 32.4%& x202f;+/- 11.2% after DCB angioplasty, and 25%& x202f;+/- 16% at follow-up. Stenosis over 50% was present in 3 lesions during the follow-up period (8.3%, 3/36). Conclusion In this study, the application of DCBs to treat ICAD patients was feasible and safe. A larger scale clinical trial is warranted to further evaluate the safety and efficacy of this treatment.