The safety and patency of endovascular treatment (EVT) in isolated common femoral artery (CFA) and popliteal artery (PA) remain poorly understood. We investigated the efficacy after EVT for isolated CFA and PA disease. This study was performed as a multicenter retrospective registry of a prospectively maintained database. Between January 2001 and December 2010, consecutive 183 patients (214 lesions; CFA 111, PA 103) who received endovascular procedure for de novo isolated CFA and PA disease were enrolled. The main endpoints of this study were primary and secondary patency after EVT. Procedure success was 95.8 %. The 1- and 5-year primary patencies for CFA (PA) lesions after EVT were 73.5 % (75.5 %) and 46.9 % (56.2 %), respectively. There was no significant difference of primary patency rate between CFA and PA (46.9 vs. 56.2 % at 5-year, p = 0.83). However, secondary patency significantly differed between CFA and PA (97.6 vs. 86.2 % at 5-year, p = 0.009). Stent placement was not effective for the reduction of restenosis in both CFA and PA lesion. On multivariate analysis to define the predictors of primary patency for the CFA, renal failure, coronary artery disease, calcified lesion and residual stenosis after EVT were independent predictors. Also, the predictors of primary patency for the PA were BMI, reference vessel diameter, anemia and residual stenosis after EVT. Short-term patency after EVT for isolated CFA and PA lesion seems to be feasible. However, long-term patency was not promising. Furthermore, stent placement does not improve the primary patency.