Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is an increasingly adopted life-saving mechanical circulatory support for a number of potentially reversible or treatable cardiac diseases. It is also started as a bridge-to-transplantation/ventricular assist device in the case of unrecoverable cardiac or cardio-respiratory illness. In recent years, principally for non-post-cardiotomy shock, peripheral cannulation using the femoral vessels has been the approach of choice because it does not need the chest opening, can be quickly established, can be applied percutaneously, and is less likely to cause bleeding and infections than central cannulation. Peripheral ECMO, however, is characterized by a higher rate of vascular complications. The mechanisms of such adverse events are often multifactorial, including suboptimal arterial perfusion and hemodynamic instability due to the underlying disease, peripheral vascular disease, and placement of cannulas that nearly occlude the vessel. The effect of femoral artery damage and/or significant reduced limb perfusion can be devastating because limb ischemia can lead to compartment syndrome, requiring fasciotomy and, occasionally, even limb amputation, thereby negatively impacting hospital stay, long-term functional outcomes, and survival. Data on this topic are highly fragmentary, and there are no clear-cut recommendations. Accordingly, the strategies adopted to cope with this complication vary a great deal, ranging from preventive placement of antegrade distal perfusion cannulas to rescue interventions and vascular surgery after the complication has manifested.This review aims to provide a comprehensive overview of limb ischemia during femoral cannulation for VA-ECMO in adults, focusing on incidence, tools for early diagnosis, risk factors, and preventive and treating strategies.