When agitating mesenchymal stem cells adhered on microcarriers in bioreactors, a compromise has to be found between sufficient particle suspension and limitation of hydromechanical stresses. The present study proposes a strategy to improve the design of an 'elephant ear' impeller at the just-suspended state by varying its relative size, blade slope angle, and position in the reactor. To do that, computational fluid dynamics simulations were coupled with multi-objective optimization to minimize the hydromechanical stress encountered by the microcarriers. Two minimization criteria were considered: (P/V)(@p) and the energy dissipation function EDC. On the basis of 31 conditions, an optimal impeller geometry is proposed.