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Orbitally shaken bioreactors are an emerging alternative to stirred-tank bioreactors for large-scale mammalian cell culture, but their fluid dynamics is still not well defined. Among the theoretical and practical issues that remain to be resolved, the characterization of the liquid free surface during orbital shaking remains a major challenge because it is an essential aspect of gas transfer and mixing in these reactors. To simulate the fluid behavior and the free surface shape, we developed a numerical method based on the finite element framework. We found that the large density ratio between the liquid and the gas phases induced unphysical results for the free surface shape. We therefore devised a new pressure correction scheme to deal with large density ratios. The simulations operated with this new scheme gave values of wave amplitude similar to the ones measured experimentally. These simulations were used to calculate the shear stress and to study the mixing principle in orbitally shaken bioreactors. Copyright (C) 2012 John Wiley & Sons, Ltd.