Venovenous extracorporeal membrane oxygenation (VV ECMO) serves as a last resort intervention for critically ill patients with acute respiratory distress syndrome (ARDS), when conventional treatments fall short. The treatment involves extracting blood from the patient, oxygenating it via a membrane and subsequently reinfusing the oxygen rich blood to the patient’s venous system, thus working as respiratory support for the patient. As cannulation strategies vary, Computational Fluid Dynamics (CFD) analyses provide valuable information on performance beyond the limitations found when employing in vivo studies. In this study, we compare femoro-femoral (FF) cannulation to the previously studied femoro-atrial (FA) and atrio-femoral (AF) cannulation [1]. For FF cannulation, both return and drainage cannulas are inserted in each femoral vein, draining and returning the blood in the inferior vena cava (IVC) and thus eliminating the need of cannulation in the upper body. Computer aided design models were created based on a previously published patient-averaged model [1]. Cannulas selected for drainage and return of blood were the Maquet HLS Multistage 25Fr/55cm cannula and the Medtronic Bio-Medicus FLEX 21Fr/55cm cannula, selected by the ECMO team at Karolinska University Hospital. Large-Eddy Simulations (LES) were run at ECMO flow rates ranging from 2 – 6 L/min, applying a non-Newtonian Quemada viscosity model. Findings were that FF cannulation displayed lower recirculation fraction (oxygenated ECMO return flow directly drained back into the ECMO circuit) than AF for all ECMO flow rates, however higher than FA. Velocity streamlines displayed a large rotating vortex in the centre of the right atrium, similar to that occurring without cannulation. In addition, substantial negative pressures were found in the IVC under high flow rates which may lead to collapse of the vessel in a real-life scenario. Further, elevated levels of shear stress were observed, which may increase the risk of coagulation in the patient.