Background and Aims Critical limb ischemia (CLI) represents the end stage of lower extremity arterial disease. Infrapopliteal artery lesions, due to their complex anatomical and pathological characteristics, pose significant therapeutic challenges, with patients facing high rates of amputation and mortality. In recent years, endovascular treatment techniques have evolved rapidly; however, controversy remains regarding the optimal treatment strategy. To systematically compare the efficacy of different treatment modalities, this study conducted a network Meta-analysis to comprehensively evaluate balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), and orbital atherectomy (OA) in the treatment of CLI involving infrapopliteal artery lesions, providing evidence to guide clinical decision-making on optimal endovascular therapy.Methods A comprehensive search of multiple medical databases was performed, and 17 randomized controlled trials with a total of 2 379 patients were included. A network Meta-analysis was conducted. The primary outcomes were 1-year primary patency rate, target lesion revascularization (TLR) rate, and major amputation rate.Results DCB showed the highest efficacy in 1-year primary patency, significantly outperforming DES (OR=4.55, 95% CI=1.14-20.00), BMS (OR=15.77, 95% CI=3.50-71.00), and BA (OR=9.02, 95% CI=2.43-33.47). DCB also demonstrated the lowest 1-year TLR rate, significantly lower than BA (OR=0.40, 95% CI=0.22-0.72). There were no statistically significant differences among treatment methods in terms of the 1-year major amputation rate; however, the cumulative ranking analysis suggested that DES may be the most effective in reducing major amputation risk.Conclusion DCB offers clear advantages in improving primary patency and reducing TLR rates, while DES may be the most effective strategy for reducing the risk of major amputation. DCB and DES should be prioritized in the endovascular treatment of CLI involving infrapopliteal artery lesions.