Objectives: The aim of this study was to evaluate the 24-month outcome of Drug-Coating Balloon (DCB) versus Bare-metal stent (BMS) for the treatment of disabling claudication and critical limb ischemia in patients with complex femoropopliteal lesions regarding technical success, primary patency, secondary patency, target lesion revascularization (TLR) and limb salvage rate. Background: Complex femoropopliteal lesions are difficult to treat and the effective protocols for intervention remain to be developed. Patients and methods: This study is a multi-center, prospective, randomized controlled two-arm blind interventional study. Eighty patients (92 limbs) complaining of disabling claudication or critical limb ischemia due to complex femoropopliteal occlusive lesions have been randomly assigned into two groups according to the intervention approach used from May 2016 to August 2020. Group A included 42 patients (47 limbs) who have been assigned for treatment with paclitaxel DCBs and group B included 38 patients (45 limbs) assigned for treatment with BMSs. The follow-up period was for 24 months with regular visits at 3,6,9, 12,15, 18 and 24 months or when new concerns have emerged. All data were analyzed by using Statistical Package of Social Science for windows version 22.0 (IBM Inc., Chicago, IL, USA) and MedCalc windows (MedCalc Software bvba 18, Ostend, Belgium). Results: The 1-year primary patency rates in the DCB and BMS groups were 87.2% and 75.6% (p = 0.15), respectively, and the corresponding 2-year rates were 76.6% and 57.8 (p = 0.05). While the 1-year secondary patency rates in the DCB and BMS groups were 95.7% and 91.1% (p =0.43), respectively, and the corresponding 2-year rates were 91.4% and 75.5% (p =0.05). There is statistically significant difference of primary and secondary patency at 24 months between both groups (p=0.05). The 2-year major limb amputation rate was 6.3% in DCB group versus 11.1% in BMS group (p = 0.48), which was statistically insignificant. The post-procedural ABI shows highly significant difference between both groups at 24 months, (p <0.001). Conclusions: The two years outcomes showed superior efficacy, higher safety and greater clinical benefits of DCBs than BMSs for the treatment of complex femoropopliteal lesions. A statistically significant lower rate of restenosis, occlusions and statistically significant higher 2-year primary and secondary patency rates were observed in the DCB group than in the BMS group. However, more studies with a larger sample and long-term follow-up are required.