With the increasing importance of minimizing primary energy usage and complying with emission restrictions, a significant interest has been developed towards waste heat recovery from industrial processes. A large portion of this energy is available at low temperatures (350K–400K) but it can be relatively efficiently converted into mechanical power using an Organic Rankine Cycle (ORC). Twin screw expanders can be used as an alternative to turbines with their cheap production costs and well proven efficiencies. In this paper, 3D CFD simulations of a twin screw expander using R245fa as the working fluid are performed. Since the fluid properties show big deviations when using the ideal gas equation of state (EoS), the flow problem has been evaluated using different real gas models. Thermodynamic parameters for the ideal gas EoS, the cubic Aungier Redlich-Kwong EoS and the CoolProp fluid database (open source) were compared in a preliminary study. After that, the models have been included through user-defined functions (UDFs) in ANSYS Fluent and were tested on 3D CFD calculations of a twin screw expander and a simplified expansion model. Several performance indicators such as mass flow rates, pressure-volume diagrams and power output are used to compare different fluid models for R245fa. From the results of this study, it can be concluded that the ideal gas EoS shows big deviations going closer to the saturation vapor line and the deviation in power comparing to the Aungier Redlich-Kwong EoS is around 8%. Conversely, the Aungier Redlich-Kwong EoS and the CoolProp database present very similar results for this case.