To identify anatomical factors associated with major adverse limb events (MALE) after angioplasty as the basis for a novel morphology-driven classification of infrapopliteal lesions.Retrospective-multicenter study.Between March 2004 and October 2010, 1057 limbs from 884 patients with CLI due to isolated infrapopliteal lesions were studied. Freedom-from MALE, defined as major amputation or any reintervention, was assessed out to 2 years by the Kaplan-Meier methods. Anatomical predictors and risk stratification for MALE were analyzed by multivariate analysis.Freedom-from MALE was 47 ± 1% at 2 years. Lesion calcification, target vessel diameter300 mm and no below-the-ankle (BA) run-off were positively associated with MALE by multivariate-analysis. The total number of risk factors was used to calculate the risk score for each limbs for subsequent categorization into 3 groups with 0 or 1 (low-risk), 2 (moderate-risk) and 3 or 4 (high-risk) factors. Freedom-from MALE at 2 year-rates was 59% in low-risk, 46% in moderate-risk, and 29% in high-risk, respectively.Target vessel diameter 300 mm and no-BA run-off were associated with MALE after infrapopliteal angioplasty. Risk stratification based on these predictors allows estimation of future incidence of MALE in CLI with isolated infrapopliteal lesions.