Patients with left main or multivessel coronary artery disease (CAD) and depressed left ventricular function undergoing coronary artery by-pass grafting (CABG) have a markedly worse prognosis compared with general population. As a consequence, these patients are often refused for surgical revascularization. At the same time, surgical ineligibility is associated with poor clinical outcome when these patients are referred for percutaneous coronary intervention (PCI). However, recent studies suggest that a revascularization strategy with a protected percutaneous coronary intervention (PCI) using a mechanical assistance device may be a viable alternative. In particular, the development of percutaneous left ventricular assist devices such as Impella has been an important step to facilitate the care of these high-risk patients. In this review we discuss about conditions for surgical ineligibility and the clinical outcome of PCI in high-risk patients ineligible for surgery. Moreover, we discuss about the evidences supporting the use of Impella in high-risk patients ineligible for surgery.