Objective To assess the efficacy and safety of drug-coated balloon (DCB) treatment for femoralpopliteal arteriosclerosis occlusion.Methods A retrospective analysis was conducted of 162 patients treated in our hospital from June 2016 to May 2017 with femoralpopliteal artery disease (Rutherford 2-4). The patients were classified as DCB group (n=102) treated with DCB and PTA group (n=60) with percutaneous transluminal angioplasty (PTA). The patients were followed up and evaluated at 30 days, 6 months and 12 months after operation. Basic information was collected, and efficacy endpoints and safety endpoints were analyzed for both groups. SPSS statistics 19.0 was used for data analysis, and independent samples t test, Chi-square test (Pearson Chi-square or four-fold contingency table) or Wilcoxon signed-rank test were used for comparison. Results No significant difference between the 2 groups was observed in the basic data, but the male and the smokers in both groups accounted for above 50%. There was no significant difference between the 2 groups (P>0.05) in the characteristics of lesion and operation-associated variables. At 12 months follow-up, DCB group had a significantly greater increase than the PTA group in the primary patency rate [76.5%(78/102) vs 56.7%(34/60),P=0.008] and ankle brachial index (ABI) [(0.89±0.14) vs (0.82±0.20), P=0.027] and a significantly greater decrease in the ratio of target lesion revascularization (TLR) [5.9%(6/102) vs 27.1%(16/60), P<0.001]. However, the DCB group did not differ significantly than the PTA group in improved walking impairment questionnaire (WIQ) score [22.3(8.0,9.4) vs 21.4(5.4,7.7),P=0.403] and success rate of operation [100%(102/102) vs 100%(60/60), P=1.000]. One man in DCB group died of severe chronic obstructive pulmonary disease with severe pulmonary infection after 6 months′ follow-up, and one diabetic patient in PTA group underwent lower knee amputation for severe infection following foot trauma also after 6 months′ follow-up, but there was no significant difference between 2 groups in the incidence of safety endpoints and main adverse events (P>0.05). Conclusion DCB shows superior outcomes over PTA in the treatment of de novo femoropopliteal arteriosclerosis occlusion with comparable safety.