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BackgroundLower extremity arterial disease (LEAD) remains a major cause of amputation, even after successful endovascular revascularization therapy (EVT). The prognostic associations of the pan-immune inflammatory value (PIV) and fibrinogen-to-albumin ratio (FAR) in LEAD remain unclear. This study investigated the associations of PIV and FAR with amputation risk and evaluated their incremental prognostic value beyond established clinical variables.MethodsIn this multicenter retrospective cohort study, 1,082 patients with LEAD who underwent EVT at four tertiary hospitals in Southwest China between January 2018 and July 2023 were analyzed. Restricted cubic spline (RCS) analyses and Cox proportional hazards regression models were used to evaluate the associations of PIV and FAR with amputation risk. Exploratory cut-off values were derived using receiver operating characteristic (ROC) curve analysis. The incremental prognostic value of adding PIV and FAR to clinical variables was assessed using time-dependent ROC analysis.ResultsDuring a median follow-up of 31 months, 198 (18.3%) patients experienced amputation. RCS revealed significant nonlinear associations of PIV and FAR with amputation risk (p for nonlinearity < 0.001). After multivariable adjustment, higher levels of both biomarkers remained independently associated with increased amputation risk (Z-PIV: HR = 1.379; Z-FAR: HR = 1.176; both p < 0.001). The addition of PIV and FAR to the clinical model enhanced time-dependent discrimination; the AUC(t) increased from 0.771 to 0.819 at 1 year, 0.766 to 0.806 at 2 years, and 0.762 to 0.807 at 3 years (all adjusted p < 0.001). Fine-Gray competing-risk analyses yielded consistent results after accounting for death as a competing event.ConclusionPIV and FAR were independently associated with amputation risk in patients with LEAD who underwent EVT. The addition of these biomarkers to established clinical variables provided incremental prognostic value and may offer additional prognostic information for risk stratification.