This research describes a simulation based on three dimensional computational fluid dynamics (CFD) in a semi-continuous PFR reactor. The commercial software FLUENT 6.3 was employed to solve the governing equations. The gas-liquid flow was modeled using an Eulerian multiphase and k-ε turbulence (RNG) model. Hydrodynamics investigated for different total solid (TS) levels and mixing regime using multiple reference frame (MRF) model within the whole multiphase bioreactor. The simulation results in a prototype reactor are validated against the experimental data. Simulation results indicate that flow pattern within the reactor was highly influenced by the substrate density and viscosity, and stirring intensity. Moreover, substrate density and viscosity are variable according to the TS content. The results demonstrate adequate mixing process providing the required amount and intensity of mixing for uniform distribution of reactor content and needed conditions to improve the reactor performance. Comparison of three impeller mixing speed in a reactor demonstrates that mixing intensity has affected the gas phase above the fluid surface. Such a mixing intensity may create a turbulent region with a homogenous mixture of gas and liquid, which is not suitable for this anaerobic digestion.