Purpose To assess superiority of paclitaxel drug-coated balloons (DCB) in prevention of neointimal hyperplasia and restenosis after treatment of symptomatic superficial femoral artery (SFA) occlusive lesions. Background Endovascular treatment (ET) has become the first choice for SFA atherosclerotic lesions. Despite enhanced immediate technical success, neointimal hyperplasia and restenosis remain the Achilles heel of ET. Patients and methods This prospective randomized controlled two-arm blind interventional study was conducted on 134 patients with symptomatic SFA atherosclerotic lesions. Patients were randomly allocated by using simple random allocation method, where 134 cards were used for allotment of cases into two groups (67 patients were assigned to group A, in which patients were subjected to treatment with paclitaxel DCB and other 67 were assigned to group B, where patients were subjected to treatment with plain old balloon angioplasty). Follow-up was for 2 years. Results Primary patency and limb salvage after 1 and 6 months were statistically insignificant in both groups (P=0.21 and 0.19 and 0.049 and 0.051, respectively), but after 12 and 24 months, primary patency and limb salvage were statistically highly significant in group A (P=0.0018 and 0.0011 and 0.0019 and 0.0023, respectively). Conclusion ET with DCB has equal risks but higher antirestenotic efficacy than plain old balloon angioplasty in femoropopliteal artery disease. The use of DCB increases patency and limb salvage. Stenting still has a rising role in bail-out in the treatment of SFA occlusive disease and is associated with better acute angiographic results.