Abstract: There is no effective strategy for preventing or treating myocardial ischemia-reperfusion (MI/R) injury. A recent set of basic and clinical research indicates that implanting a percutaneous ventricular assistance device (pVAD) prior to reperfusion unloads the ventricle and decreases myocardial oxygen consumption. The ventricular unloading induced by pVAD implantation prevents the infarction enlargement and minimizes fibrotic scar formation. The implantation of pVAD before reperfusion is recognized as a promising therapeutic approach for ameliorating MI/R injury. We summarize the application and mechanism of pVAD-induced ventricular unloading in the prevention and treatment of MI/R injury.