Objective Interventions for multilevel critical limb ischemia include endovascular and surgical bypass revascularization. A hybrid approach combining both techniques is progressively used worldwide. The present randomized study proposed to compare the postoperative and clinical outcomes of surgical bypass and hybrid approach in patients with multilevel critical lower limb ischemia. Patients and methods This clinical randomized study was conducted in the period from September 2014 through April 2019. The study included 52 patients with multilevel critical limb ischemia. Patients were subjected to open surgical bypass (n=29) or hybrid intervention (n=23). Assessment included clinical examination, ankle-brachial pressure index measurement, arterial duplex (including ankle peak systolic velocity), and computed tomography angiography. Postoperatively, patients were followed at 1, 3, 6, 12 months, and then annually. The primary outcome in the present study was patency (primary, primary assisted, and secondary). Other outcome parameters included technical success (residual stenosis <30%), postoperative complications, ICU admission, hospital stay, major amputation, and mortality. Results Technical success was achieved in all the studied patients in both groups. Patients in surgical bypass group had higher rate of ICU admission and significantly longer hospital stay. In addition, they experienced significantly higher rate of postoperative wound infection and seroma formation. However, no significant differences were found between the studied groups regarding primary patency (62.1 vs. 60.9%, P=0.93), primary assisted patency (75.9 vs. 69.6%, P=0.61), secondary patency (86.2 vs. 87.0%, P=0.94), major amputation (13.8 vs. 13.0%, P=0.94), and mortality (10.3 vs. 4.3%, P=0.42). Conclusion Hybrid intervention provides patency and limb salvage rates equivalent to Open surgery. Moreover, the hybrid approach is associated with lower need of ICU admission and shorter hospital stay, which can reduce the clinical resource utilization.