Abstract: Objective To compared the efficacy of drug-coated balloon and common balloon for treatment of superficial femoral artery and popliteal artery occlusive disease. Methods Forty-six patients were admitted for ipsilateral single or multiple superficial femoral artery and/or popliteal artery lesions (between 3 and 15 cm stenosis or occlusion), Rutherford grades 2 to 5, with or without other accompanying diseases in the Department of Interventional Vascular Therapy of the First Hospital of Nanjing between September, 2015 and December, 2016. The patients were randomly assigned into drug-coated balloon (DCB) group (n=23) and common balloon (CB) group (n=23). None of the patients had stent restenosis, aneurysms, acute thrombosis, pregnancy, life expectancy less than 1 year, or below-the-knee artery occlusion. The late lumen loss (LLL), improvement of the ankle brachial index (ABI), improvement of Rutherford grade, incidence of restenosis, thrombosis rate and amputation rate were compared between the two groups at 6 months after treatment. Results The two groups of patients were comparable for general conditions, risk factors, and characteristics of the compromised vessels (P>0.05). Six months after treatment, the patients in DCB group showed significantly smaller LLL, more obvious improvement of the ABI and Rutherford grade, and lower restenosis rate and thrombosis rate than those in CB group (P<0.05). The amputation rates were similar between the two groups (P>0.05). Conclusions DCB shows obvious advantages over common balloon for treatment of superficial artery and popliteal artery arteriosclerosis obliterans in that it more effectively reduces LLL, restenosis rate and thrombosis rate and improves the ABI and Rutherford grade at 6 months after the treatment.