Background: The purpose of this study was to determine the efficacy of interventional endovascular treatment (EVT) and the risk factors for postoperative restenosis in patients with Trans-Atlantic Inter-Society Consensus (TASC) II C/D femoropopliteal lesions. Methods: A total of 55 patients who received EVT for TASC ? C/D femoropopliteal lesions (64 affected limbs) from October 2014 to September 2017 were examined. The mean lesion length was 19.6±5.3 (range, 15.5-26.4 cm). The femoropopliteal lesions were classified as TASC ? C and TASC ? D in 39 and 16 cases, respectively. The ankle-brachial index (ABI), primary patency rate, secondary patency rate, and limb salvage rate were monitored in follow-up evaluations for up to 24 months. A Cox regression model was used to evaluate the correlation between each of these factors and the restenosis rate after EVT. Results: Patent TASC ? C/D femoropopliteal lesions were present in 59 of the 64 limbs. The mean ABI values for the dorsal pedal artery and posterior tibial artery increased 1 month after treatment from a baseline level of 0.35±0.12 to 0.89±0.10 and from 0.43±0.15 to 0.90±0.13, respectively (P<0.01). The mean follow-up time was 19.3 (range, 6-24) months. The cumulative primary patency rates at 1, 3, 6, 12, 18, and 24 months were 98.3%, 91.5%, 84.3%, 61.1%, 53.1%, and 31.1%, respectively. The secondary patency rates at 12 and 24 months were 70.4% and 60.0%, respectively. Factors with a high hazard ratio included male sex, TASC II D, smoking, and diabetes mellitus (DM). Conclusions: EVT had a safe and satisfactory mid-term therapeutic effect on TASC II C/D femoropopliteal lesions. Male sex, TASC II D (compared to TASC II C), smoking, and DM were risk factors for restenosis. EVT has a secondary patency rate comparable to that of open surgery and can be considered a first-line treatment for TASC II C/D femoropopliteal lesions. © 2021 AME Publishing Company. All rights reserved.