Abstract: Objective To evaluate the efficacy and safety of drug-coated balloon (DCB) angioplasty versus uncoated balloon (UCB) angioplasty in treatment of lower extremity arterial occlusive disease (LEAOD). Methods Randomized controlled trial comparing DCB and UCB angioplasty for treatment of LEAOD were searched in online databases. Literature screening and quality assessment was carried out according to the established inclusion criteria and exclusion criteria. Restenosis rate at 6 months after surgery, late lumen loss, target lesion revascularization rate, patency rate, mortality rate, and amputation rate at 1 year after operation were compared between DCB group and UCB group using RevMan 5.3 software. Results Eleven trials involving a total of 1853 patients with 2150 lesions were included, with 1110 patients (1288 lesions) in DCB group and 743 patients (862 lesions ) in UCB group. Meta-analysis showed that the restenosis rate at 6 months after the operation (15.2% vs 39.0%; OR: 0.28; 95%CI: 0.17 to 0.48; P<0.00001), late lumen loss (range -0.05 to 0.56 vs 0.54 to 1.7; WMD: -0.57; 95%CI: -0.93 to -0.21), and target lesion revascularization rate at 1 year after operation (13.0% vs 28.1%; OR: 0.39; 95%CI: 0.23 to 0.64; P= 0.0002) were significantly lower in DCB group than in UCB group. The patency rate at 1 year after the operation was significantly higher in DCB group than in UCB group (71.8% vs 52.9%; OR: 2.32; 95%CI: 1.21 to 4.43; P=0.001). The mortality rate (4.8% vs 5.0%; OR: 1.00; 95%CI: 0.62 to 1.63; P=0.99) and amputation rate at 1 year after the operation (3.4% vs 2.9%; OR: 1.41; 95%CI: 0.74 to 2.70; P=0.30) did not differ significantly between DCB and UCB group. Conclusion DCB angioplasty is more effective than UCB angioplasty in endovascular treatment of LEAOD with similar treatment safety.