The screw expander discussed in this work was part of a 50 kW organic Rankine cycle (ORC) system. The ORC was tested under different conditions in heat source and heat sink. In conjunction with collecting data for the ORC system, experimental data were also collected for the individual components of the ORC, viz. evaporator, preheater, screw expander, working fluid pump, and condenser. Experimental data for the screw expander were used to develop the two empirical models discussed in this paper for estimating screw expander performance. As the physical parameters of the screw expander discussed in this article are not known, a “black-box” approach was followed to estimate screw expander power output, based on expander inlet and outlet pressure and temperature data. Refrigerant R245fa was used as the working fluid in the ORC. The experimental data showed that the screw expander had ranges of pressure ratio (2.70 to 6.54), volume ratio (2.54 to 6.20), and power output (10 to 51.5 kW). Of the two empirical models, the first model is based on the polytropic expansion process, in which an expression for the polytropic exponent is found by applying regression curve-fitting analysis as a function of the expander pressure ratio and volume ratio. In the second model, an expression for screw expander work output is found by applying regression curve-fitting analysis as a function of the expander isentropic work output. The predicted screw expander power output using the polytropic exponent model was within ±10% of experimental values; the predicted screw expander power output using the isentropic work output model was within ±7.5% of experimental values.