Objective The objective of this study was to provide a systematic review and meta-analysis of outcomes of infrainguinal angioplasty with drug-eluting stent (DES) or balloon (DEB). Methods The EMBASE, MEDLINE, and Cochrane databases and the Current Controlled Trials register were systematically interrogated for articles reporting results of infrainguinal angioplasty with DESs or DEBs. Clinical and angiographic end points were included. Results The review included 26 studies that reported on 2407 limbs; 11 were prospective randomized controlled trials. Infrapopliteal angioplasty with DEB was reported in 109 limbs (claudication, 19; critical limb ischemia [CLI], 90) (limb salvage in CLI, 95.6%; target lesion revascularization [TLR], 17.3%; mortality, 16%; mean follow-up, 12.3 months). Infrapopliteal angioplasty with DES was reported in 882 limbs (claudication, 160; CLI, 590; unclear severity, 132) (limb salvage in CLI, 97.4%, TLR, 10.8%; mortality, 17%; mean follow-up, 22.9 months). Femoropopliteal angioplasty with DES was reported in 1174 limbs (claudication, 301; CLI, 58; unclear severity, 815) (limb salvage in CLI, 89.6%; TLR, 17.3%; mortality, 3%; mean follow-up, 10.6 months). Femoropopliteal angioplasty with DEB was reported in 242 limbs (claudication, 182; CLI, 12; unclear severity, 48) (TLR, 10.6%; mortality, 2%; mean follow-up, 11 months). Meta-analysis of studies comparing DEB with standard balloon angioplasty demonstrated a result in favor of DEBs for preventing binary primary restenosis (odds ratio [OR], 0.27; P = .005) and TLR (OR, 0.17; P = .001). The meta-analysis comparing DESs with bare-metal stents demonstrated a result in favor of DES with regard to preventing TLR (OR, 0.15; P = .001) and binary primary restenosis (OR, 0.23; P = .001). Drug-eluting technology did not prevent more deaths or amputations. Conclusions Early angiographic data suggest that drug-eluting devices prevent restenosis in the short term, but there is as yet no evidence of an increase in limb salvage rates or a reduction in mortality. Further large randomized controlled trials with a focus on clinical outcomes and longer follow-up are needed.