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Background: The relative merits of the drug-coated balloon (DCB) versus uncoated balloon (UCB) angioplasty in endovascular intervention for patients with symptomatic lower extremity peripheral arterial disease (PAD) remains controversial.Methods: Online databases were queried with various combinations of keywords to identify relevant articles. Net adverse events (NAEs) and its components were compared using a random effect model to calculate unadjusted odds ratios (ORs).Results: A total of 26 studies comprising 26,845 patients (UCB: 17,770 and DCB: 9075) were included. On pooled analysis, DCB was associated with significantly lower odds of NAE (OR: 0.47, 95% confidence interval [CI]: 0.36-0.61), vessel restenosis (OR: 0.46, 95% CI: 0.37-0.57), major amputation (OR: 0.68, 95% CI: 0.47-99), need for repeat target lesion (OR: 0.38, 95% CI: 0.31-0.47) and target vessel revascularization (OR: 0.62, 95% CI: 0.47-0.81) compared with UCB. Similarly, the primary patency rate was significantly higher in patients undergoing DCB angioplasty (OR: 1.44, 95% CI: 1.19-1.75), while the odds for all-cause mortality (OR: 0.96, 95% CI: 0.85-1.09) were not significantly different between the two groups. A subgroup analysis based on follow-up duration (6 months vs. 1 vs. 2 years) followed the findings of the pooled analysis with few exceptions. Conclusions:The use of DCB in lower extremity PAD intervention is associated with higher primary patency, lower restenosis, lower amputation rate, and decreased need for repeat revascularization with similar all-cause mortality as compared to UCB.