Abstract Background Clinically driven target lesion revascularization (CD-TLR) and restenosis are common complications in individuals with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease undergoing percutaneous transluminal angioplasty (PTA). Drug-eluting balloons, stents, and resorbable scaffolds have emerged as an alternative therapy that may decrease the recurrence of these complications compared to PTA. However, their efficacy and safety are still controversial. Purpose This study aims to update and provide new insights about coated balloons, stents, and resorbable scaffolds as drug-eluting devices compared to PTA in patients with CLTI and infrapopliteal artery disease. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing drug-eluting devices, such as stents, coated balloons, and resorbable scaffolds, to PTA in patients with CLTI and infrapopliteal artery disease. The primary endpoint of interest was (1) CD-TLR. We only included trials defining this outcome as angiographically confirmed restenosis associated with wound changes or change in Rutherford classification at 12 months follow-up. This study also reported the following secondary outcomes: (2) binary restenosis and (3) amputation. We performed a subgroup analysis of the drug-eluting devices and between the drug-eluting pharmacological class, comparing the limus drug family subgroup and Pactlitaxel subgroup. Results We included 6 RCTs, encompassing 1263 patients, of whom 761 (60.2%) received a drug-eluting device. The mean age was 70.94 years. In the pooled analysis, the primary endpoint of CD-TLR was not statistically significant(OR 0.79; 95% CI 0.56-1.12; p=0.64; figure 1A). Although binary restenosis (OR: 0.62; 95% CI 0.36-1.05; p= 0.04; Fig.1B) was not statistically significant, our subgroup analysis of different drug-eluting pharmacological classes was significantly different(p<0.01; Fig.1B). Furthermore, the -limus family subgroup presented with a significant lower (OR 0.39; 95% CI 0.25 - 0.61; p<0.01; Fig. 1B) binary restenosis. There was no significant difference in the amputation endpoint (OR: 1.12; 95% CI 0.52 - 2.49; p= 0.74) and among the drug-eluting devices subgroup (p=0.63; Fig. 1A) for the CD-TLR endpoint. Conclusion In this updated meta-analysis of patients with CLTI and infrapopliteal artery, drug-eluting devices were not associated with CD-TLR compared to PTA. However, the -limus drug family is associated with a more significant reduction in the binary restenosis endpoint.