High-risk percutaneous coronary interventions (PCI) are used to treat patients with severe coronary artery disease (CAD) and significant comorbidities that make traditional approaches particularly challenging. Patients involved are with multi-vessel disease, at risk for hemodynamic instability, left ventricular dysfunction. In such high-risk cases, maintaining adequate systemic circulation and myocardial perfusion is critical. These clinical scenarios are where the use of mechanical circulatory support (MCS) devices, such as the Impella device, are useful. Impella CP with SmartAssist is a microaxial pump inserted percutaneously through the femoral artery until it crosses the aortic valve and reaches the left ventricle. Therefore, the presence of peripheral artery disease (PAD), which commonly coexists with CAD, can further complicate these interventions. We present the case of a 76-years old male patient with history of hypertension, dyslipidemia, permanent atrial fibrillation, prostatectomy, previous abdominal aortic aneurysm and aorto-bisiliac bypass surgery and severe peripheral artery disease who presented with dilated cardiomyopathy and severe LV systolic dysfunction (ejection fraction, EF 30%). At coronary angiography a critical tree vessel coronary artery disease with critical involvement of the distal left main was found. After discussion in Heart Team percutaneous revascularization with the hemodynamic support using Impella was planned. A CT angiogram scan prior to Impella was performed to evaluate the aorto-iliac-femoral axis that confirmed the replacement of the infrarenal aorta and the aorto-bisiliac bypass with patency of the right and left prosthetic branches with an occlusion of the left iliac artery and 70% stenosis of the right iliac artery (Fig 1). PTA of the right iliac artery was performed with stent implantation (Luminex 9×60 mm) (Fig2). Subsequently we crossed the iliac stent with the 14 French 25 cm peel-away introducer sheath (Fig 3) and placed the Impella pump across the aortic valve. The PCI was then successfully performed stenting the obtuse marginal branch and the left main–proximal LAD. Conclusion: The use of the Impella device in patients with peripheral artery disease undergoing high-risk percutaneous coronary interventions can be challenging. Careful patient selection and study of the aorto-iliac femoral axis are essential to ensure the benefits of this advanced mechanical support system minimizing potential risks.