Objective: To investigate the efficacy of paclitaxel-eluting drug-coated balloon (DCB) in treatment of atherosclerosis obliterans (ASO) of the lower extremities. Methods: Twenty-eight eligible patients with femoropopliteal disease were enrolled to study. All patients had moderate or severe intermittent claudication or ischemic rest pain (Rutherford grade 2–4), the degree of stenosis ranging from 70% to 99%, and simultaneously with length of lesion between 4 and 20 cm or occlusive lesion ≤10 cm involving the superficial femoral artery to proximal popliteal artery. Of the patients, 17 cases received DCB treatment (DCB group), and 11 cases received bare metal stent (BMS) implantation (BMS group). The end-point measurements of the main efficacy were the patency rates, and revascularization and restenosis in the region of the target lesion at 12 months after operation. Results: There was no statistical difference in all clinical variables between the two groups before operation (all P>0.05). At follow-up 12 months after operation, the primary patency rates between DCB group and BMS group showed no significant difference (88.2% vs. 72.7%, P=0.35), but the revascularization rate in the region of the target lesion in DCB group was significantly better than that in BMS group (5.9% vs. 45.5%, P=0.02). In both groups, no intraoperative or procedure-related death occurred and no major amputation was required. The thrombosis formation rate in the region of the target lesion in DCB group and BMS group was 5.9% and 9.1%, respectively. The functional improvements of the two groups were similar at follow-up 12 months later. Conclusion: DCB has a good clinical efficacy in treatment of ASO of the lower limbs, and is not inferior to BMS in terms of patency rate and restenosis prevention as well as safety. DCB may be an important therapeutic alternative for patients with femoropopliteal lesions.