BACKGROUND: Endovascular treatment (EVT) for femoropopliteal artery disease is common in clinical practice. However, little is known about its prognostic factors, causes of death, and long-term clinical outcomes. METHODS: Two hundred eighty-five consecutive patients (mean age, 72±8 years, 73% men) undergoing their first EVT for de-novo femoropopliteal artery disease from 2009 to 2018 were studied. Patients were divided in two groups according to the presence of critical limb ischemia (CLI). We evaluated the incidence of major adverse limb events (MALE) including clinically driven target vessel revascularization and target limb major amputation, and all-cause death. RESULTS: The procedure was successful in 97.9% of cases. The non-CLI group comprised 205 patients (72%), and the CLI group comprised 80 patients (28%). The CLI group exhibited higher high-sensitivity C-reactive protein (hs-CRP) levels and a higher rate of hemodialysis than the non-CLI group. During the median follow-up period of 3.5 years, there were 62 deaths (21.8%) including cardiovascular (32.3%), infection (32,3%), and malignancy-related (22.6%) deaths. Kaplan-Meier analysis revealed that the CLI group had a significantly higher incidence of MALE and all-cause death (log-rank, both p<0.001, respectively). The leading causes of death in the CLI group were cardiovascular- and infection-related death; the leading cause of death in the non-CLI group was malignancy-related. On multivariate Cox hazard analysis, hemodialysis, TASC II classification C/D lesions, and CLI were significant predictors of MALE (p<0.001, p=0.005, and p=0.012, respectively). Hemodialysis, age, higher hs-CRP levels, and CLI were significant predictors of all-cause death (p<0.001, p=0.003, p=0.009, and p=0.021, respectively). CONCLUSIONS: Although EVT for femoropopliteal artery disease appears feasible with a high rate of procedural success, a high incidence of MALE and all-cause death was observed. Further studies are needed to improve the outcomes in patients with CLI.