Today, intensification of anaerobic digestion is still a scientific and technical challenge. The present study proposed combined experimental and computational fluid dynamics simulations to characterize the impact of shear stress and impeller design on the biogas production after sequential additions of substrate. Liquid phase (cattle manure digestate) rheological law was experimentally determined and input in numerical simulations. The results showed that the original use of a double helical ribbon in digester allowed a significantly faster dispersion of fresh substrate than the use of a classical Rushton turbine, leading to a 50% higher methane production rate. However, with both impellers, too high agitation rates entailed a clear slow-down of production rate and a decrease in CH4 content. To avoid this loss of productivity, it was shown that the maximal value of shear stress, determined by numerical simulations, was a consistent parameter to set the upper agitation conditions in digesters.