This paper presents the experimental investigation and development of a general semi empirical scroll expander model for different working fluids. Initially, the characterization and modelling of a scroll expander with R134a working fluid is performed. The influence of key operating variables on the main performance indicators such as isentropic efficiency, filling factor and specific power are investigated. The proposed semi empirical model for the scroll expander predicts mass flow rate, mechanical shaft power and exhaust temperature at accuracies of 3%, 9% and 2 K respectively. The developed semi empirical model is then modified to accommodate different working fluids; validation of the generalization procedure is performed with experimental data using ammonia/water mixture and ammonia as working fluids. The generalized semi-empirical model predicts mass flow rate, mechanical shaft power and exhaust temperature to be less than 5%, 7% and 4 K error margin for both ammonia/water and pure ammonia working fluids. Therefore, the simulation model presented in this study can save the time and material resources for the selected scroll expander solely as a consequence of a change in the working fluid to predict the main performance indicators. © 2019 Elsevier Ltd