Abstract: Appropriate hydrodynamic conditions are crucial in photobioreactors (PBR) in order to prevent sedimentation of microalgal biomass and to ensure the uniform exposure of microalgae cells to light and nutrients. Hydrodynamic conditions are also important to guarantee efficient mass transfer and proper shear stress on the transparent walls of the PBR, which can avoid the formation of undesired biofilm. Numerical simulations based on Computational Fluid Dynamics (CFD) can assist to improve the hydrodynamic design and optimization of PBRs. In this study, CFD was used as a tool to investigate the hydrodynamics of a hybrid horizontal tubular PBR designed for microalgae cultivation and wastewater treatment. The flow regime, average circulation time and shear stress distribution in the tubes were evaluated. To establish the reliability of the simulation study, the CFD model was validated using tracer experimental tests and ultrasonic flow meter measurements. Results showed that the hydrodynamic conditions in the tubes resembled plug flow with small axial dispersion. The simulated velocity profile in the tube corresponded to the analytical velocity profile based on experimental data. Simulations also showed that, even increasing flow velocities, low velocity zones were present in some zones of the PBR. The shear stress distribution in the tubes showed values higher enough to reduce or avoid the formation of biofilm, nevertheless the shear stress value is not sufficient to remove the already formed biofilm. Based on the numerical investigation and practical evaluation, this study demonstrated that CFD is a useful tool to optimize PBR design and operation in order to enhance microalgae production and boost the scale-up of this technology.