There is still a lack of quantitative information concerning optimal blood flow in the aorta and in the carotid arteries during extracorporeal circulation (ECC). Problems are not only based on the location of the aortic cannula, they are furthermore associated with the cannula design itself and the effects on blood cells and aortic wall shear stresses. We simulated a two-phase fluid flow induced by different cannulas in the ascending aorta during ECC. Three commercially available cannulas were examined according to their influence on red blood cells (RBC). Additionally, mass flow in the carotid vessels and wall shear stresses acting on the aortic wall were evaluated. A constant volume flow of blood (3.4 L/min) was applied. Numerical results demonstrate a strong relation between the mass flow rate in the carotid vessels and the geometry of the aortic outflow cannula. RBC distributions both in the aorta and the carotid vessels changed depending on cannula geometry. Maximum blood velocities, shear stresses on the aortic wall, and the fluid mechanical load acting on RBCs varied depending on each cannula design. This numerical approach demonstrates the significant influence of the cannula design on the distribution of RBCs in the carotid vessels during ECC.