Background: Drug-eluting balloon (DEB) and drug-eluting stent (DES) have been proposed for the treatment of infrapopliteal artery disease. We performed a systematic review and meta-analysis of the current available studies investigating outcomes of DEB and DES in the treatment of infrapopliteal artery disease. Methods: Multiple databases were systematically searched to identify studies investigating the outcomes of DEB and DES in the treatment of patients with infrapopliteal artery disease. The quality of studies was assessed by Cochrane Collaboration method. The demographic data, risk factors, outcomes, and antiplatelet strategy were extracted. Results: Nine studies were identified with 707 and 606 patients in DEB/DES and standard percutaneous balloon angioplasty (PTA)/bare metal stenting (BMS) group, respectively. The risk of target lesion revascularization (TLR; odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.23-0.63, P <.01), restenosis rate (OR = 0.30, 95% CI: 0.18-0.50, P <.01), and amputation rate (OR = 0.49, 95% CI: 0.29-0.83, P <.01) significantly decreased in the DES group. The overall survival (OR = 0.86, 95% CI: 0.56-1.32, P =.50) was similar in DES and standard PTA/BMS group; TLR (OR = 0.59, 95% CI: 0.32-1.09, P =.09), restenosis rate (OR = 0.49, 95% CI: 0.11-2.14, P =.35), amputation rate (OR = 1.32, 95% CI: 0.51-3.40, P =.57), and overall survival (OR = 1.40, 95% CI: 0.72-2.71, P =.32) were similar in DEB and standard PTA group. Conclusion: The present meta-analysis suggests that compared with standard PTA/BMS, DES may decrease the risk of clinically driven TLR, restenosis rate, and amputation rate without any impact on mortality. However, DEB has no obvious advantage in the treatment of infrapopliteal disease. Due to the limitations of our study, more randomized controlled trials, especially those for DEB, are necessary.