INTRODUCTION: The global burden of peripheral artery disease is increasing worldwide. A subset of 5% of these patients ultimately reach the final stage with trophic defects, a condition clinically defined as critical limb-threatening ischemia. Revascularization remains the paramount treatment modality offering the greatest potential for limb preservation. We investigated whether performing direct revascularization according to the angiosome concept significantly influences (i) the superior healing of ischemic defects, (ii) optimized limb salvage rates, and (iii) reduced patient mortality in a cohort treated with femoropopliteal bypass. METHODS: This rigorous prospective clinical cohort study processed data from 143 patients after femoropopliteal bypass procedures performed at the AGEL Ostrava Vítkovice Hospital between January 2016 and December 2021-all patients presented with critical limb-threatening ischemia, specifically Fontaine stage IV. We employed advanced statistical methods, including Kaplan-Meier survival analysis and the Cox regression model, to evaluate the effect of direct revascularization versus indirect revascularization on primary outcomes: defect healing, limb salvage, and patient mortality. RESULTS: Statistical analysis robustly confirmed a statistically significant benefit of direct revascularization on (i) defect healing (p=0.02), (ii) limb salvage (p=0.02), and (iii) patient mortality (p=0.04). Specifically, direct revascularization significantly reduced amputation rates and improved overall survival compared to indirect revascularization. CONCLUSION: Despite the controversies in the literature and the absence of dedicated, large-scale, English-language published studies focusing specifically on the application of the angiosome concept in femoropopliteal bypasses, we demonstrated a statistically significant benefit of direct revascularization on defect healing, limb salvage, and mortality in this specific patient cohort. This evidence suggests that the angiosome concept extends its predictive power proximally to the femoropopliteal bypass targets. Practical application: In patients with critical limb-threatening ischemia, where the indication for femoropopliteal bypass is rendered borderline due to advanced local findings (high-risk Wound, Ischemia, and foot Infection classification) or severe overall comorbidity status, surgical intervention should be preferentially reserved for scenarios guaranteeing direct revascularization, as patients derive minimal benefit from non-targeted indirect revascularization in high-risk settings.