For developing a scale-up method based on the kinematic and dynamic similarities of particle behavior, motion of particles in a commercial high shear mixer-granulator with different vessel sizes (2 to 112 L) were simulated using a three-dimensional discrete element method (DEM). Effects of the vessel size on the internal particle flow and the particle collision energy were analyzed. It was found that under the constant impeller tip speed magnitude of the internal particle shear flow can be nearly maintained at different vessel sizes. This implies that the constant impeller tip speed should be employed to achieve the kinematic similarity when scaling-up the high shear mixer-granulator. However, under the constant impeller tip speed the cumulative particle collision energy per unit time significantly decreased with an increase in the vessel size. This suggests that in order to achieve the dynamic similarity the granulation time should be adjusted so that the cumulative particle collision energy over the granulation time can be maintained at different vessel sizes. Based on the simulation results, we proposed a scale-up method in which the optimal granulation time can be determined to achieve the same cumulative particle collision energy at different vessel sizes while maintaining the same impeller tip speed. This method can provide both the kinematic and dynamic similarities between different vessel sizes. Validity of the proposed scale-up method was confirmed by an experiment of wet-granulation using a commercial high shear mixer-granulator with different vessel sizes (2 to 216 L). (C) 2012 Elsevier B.V. All rights reserved.