Venovenous extracorporeal membrane oxygenation (VV ECMO) can be performed with different cannulation approaches: femoro-femoral (FF), femoro-jugular (FJ), or jugulo-femoral (JF), all characterized by one drainage cannula. Dual drainage cannulation (JFF, with two drainage cannulae) may be considered in refractory hypoxemia. This work compared single vs. dual drainage concerning the impact on hemodynamics and oxygenation performance by studying the drainage ratio between the jugular and femoral cannulae, their type and position. Computational fluid dynamics was used in a patient-averaged model of the right atrium (RA) and central veins to estimate recirculation fraction (R f), arterial oxygen saturation (SaO 2), caval pressures, shear rates, time-averaged wall shear stress (TAWSS), and stagnation volume in each cannulation configuration. An ECMO flow rate of 4 L/min and cardiac output of 6 L/min were considered. JF showed the highest R f (22%) and the lowest SaO 2 (80%). The lowest R f (0.03%) and the highest SaO 2 (90%) were obtained in JFF with a multistage jugular cannula draining at a flow rate lower than the native venous inflow. FF presented the lowest pressure in the inferior vena cava (IVC, -10 mmHg), but the highest in the superior vena cava (SVC, 32 mmHg) when the return cannula tip was placed at the superior cavo-atrial junction. The stagnation volume was highest in JFF at femoral drainage ≤2 L/min. In most configurations the maximum TAWSS in the RA and SVC were more than 5 times higher than no ECMO (baseline). Adding an additional drainage cannula may in some cases improve oxygenation compared to standard single drainage configurations. The efficiency of JFF was mainly influenced by the jugular/femoral drainage ratio, cannula type and position in the SVC. Significant differences in caval pressures and TAWSS were observed between the configurations. The optimal choice of cannulation would be patient-tailored, considering specific needs and complication risks.