Peripheral arterial disease encompasses different clinical symptoms, depending on the severity of the disease. In early stages, a walking-induced pain, known as intermittent claudication, is the leading clinical symptom. Repeating cycles of ischemia and reperfusion induce a typical myopathy, with mitochondria playing the key role within this pathophysiological condition. The aim of this study is to further evaluate the effects of different treatment strategies on mitochondrial function and overall cardiovascular outcomes within a randomized controlled trial. After inclusion, patients will be randomized into different study groups. Study group 1 will receive conservative treatment, while study group 2 will receive revascularization of underlying atherosclerotic lesions. Additionally, a healthy control group will be included. Muscle biopsies will be obtained from ischemic and nonischemic muscle regions, being defined by the anatomic localization of the atherosclerotic lesion, before initiation of treatment as well as after a time interval of 12 wk. Mitochondrial function and content will be evaluated using high-resolution respirometry and citrate synthase activity measurements. Cardiovascular outcomes will be determined by established protocols. This study is registered on ClinicalTrials.gov-NCT05644158. This study aims to gain further insights into the exact pathophysiological mechanism underlying mitochondrial dysfunction in peripheral arterial disease. The potential effects of mitochondrial regeneration within ischemic muscle regions following a conservative treatment approach will be compared to those reported after revascularization procedures. Additionally, correlation with cardiovascular outcome parameters and in vivo methods will provide a comprehensive approach to this research question.