Background: The optimal endovascular method to treat infrapopliteal chronic limb-threatening ischemia (CLTI) remains to be determined, given the limitations of stent use in infrapopliteal artery disease. We performed a network meta-analysis (NWM) of randomized controlled trials (RCTs) to simultaneously compare the outcomes of different balloon angioplasty procedures for infrapopliteal artery lesions in CLTI patients.Methods: We searched the Cochrane Central Register of Controlled Trials, Embase, and PubMed. 8 eligible RCTs involving 3 endovascular modalities or combinations (plain old balloon angioplasty [POBA], drug-coated balloon [DCB], orbital atherectomy plus plain old balloon angioplasty [OA+POBA]) were included. Primary outcomes were efficacy (12-month clinically driven target lesion revascularization [CDTLR]) and safety (12-month major amputation and all-cause mortality). We used random-effects models based on the frequentist framework.Results: Plain old balloon angioplasty had a higher 12-month CDTLR rate than DCB (relative risk [RR]: 2.11, confidence interval [CI]: 1.33, 3.34) in the NWM and this result was still statistically significant (RR: 0.47, CI: 0.30, 0.75) in subgroup analyses. According to the SUCRA value, in terms of 12-month CDTLR, OA+POBA was considered the best treatment (SUCRA=72.2), while POBA was considered the worst treatment (SUCRA=8.9). In terms of 12-month all-cause mortality, OA+POBA was considered the best treatment (SUCRA=95.0), while DCB was considered the worst treatment (SUCRA=12.8). In terms of 12-month major amputation, POBA was considered the best treatment (SUCRA=72.0), while DCB was considered the worst treatment (SUCRA=23.0).Conclusions: In infrapopliteal CLTI disease, DCB showed a significantly lower 12-month CDTLR in comparison to POBA. There is no statistically significant evidence to suggest that DCB raises safety concerns. The SUCRA values of OA+POBA indicate that it might offer a superior treatment option compared to DCB or POBA in terms of CDTLR and mortality. This advantage, however, was not sustained when major-amputation rates were analyzed. Consequently, further RCTs are required to examine the potential benefits of OA and other forms of atherectomy for managing infrapopliteal CLTI disease.Clinical Impact The findings of this study provide further evidence for the safety of DCB in the application of infrapopliteal CLTI disease and suggest preliminary benefits of atherectomy. These results are likely to encourage further research and application of these treatment modalities in managing infrapopliteal CLTI.POBA has been a traditional approach for treating infrapopliteal artery disease. The current evidence supports clinicians in exploring and utilizing DCB and atherectomy as better treatments.We focused on the performance of different balloon angioplasty procedures in infrapopliteal CLTI, considering the characteristics of infrapopliteal CLTI.