Background: Despite significant improvements in endovascular technology and anaesthetic practice over the last 20 years, patients with CLTI remain at high risk of major limb amputation and overall mortality. The aim of this systematic review was to provide a contemporary review of the rate of major amputation and key clinical outcomes following all endovascular interventions in CLTI. Methods: A systematic review and meta-analysis of prospective studies from 2010-2020 reporting the risk of major lower limb amputation in patients with CLTI. MEDLINE, EMBASE, the Cochrane Database for Systematic Reviews and ClinicalTrials.gov were searched for relevant studies by 2 reviewers. The primary endpoint was rate of major limb amputation at 1 year and 2 years. Meta-analysis of proportions was employed using the random effects model. Studies were quality assessed using the ROBINS-I tool. To investigate factors associated with major limb amputations, subgroup analyses and meta-regression for clinical-demographic and lesion characteristics were employed. Results: A total of 28 studies, from 24 manuscripts were eligible for inclusion. These included a total of 49,756 patients. At one-year post-revascularisation, the pooled rate of major lower limb amputations at 1 year was 8.6% (95% CI 6.7% - 11.0%). At two years, the rate of major amputations was 11.1% (95% CI 7.6% - 16.0%). Subgroup analysis showed that in studies that mandated stent deployment for all patients, there was a significantly lower rate of major amputations of 5.1% (95% CI 4.7% - 5.5%). Meta-regression showed that none of the clinical-demographic and lesion characteristics were associated with major lower limb amputations, and no volume-outcome relationship was observed. Conclusions: This review provides important benchmarking information on the outcomes of endovascular intervention in a frail CLTI cohort. This provides a realistic evaluation of risk to facilitate full informed consent and the setting of realistic expectations regarding the need for reintervention, major and minor amputation and overall mortality.