Organic Rankine Cycle (ORC) systems represent an efficient technology for power generation from low-to medium temperature heat sources. Most of the efforts in the recent literature are addressed to the improvement of turbine design and efficiency by taking advantage of the low enthalpy drops while dealing with the large volume flow ratios across the expansion process and low speed of sound typical of high molecular weight fluids. These peculiar conditions make the choice and the design of an ORC turbine a challenging task, exacerbated by the only few experimental data available in the open literature. The aim of this paper is to obtain the optimum design and corresponding maximum efficiency of single stage radial inflow turbines for different cycle design specifications (i.e., mass flow rate and enthalpy drop) using the real gas properties of refrigerant R245fa. This aim is pursued by means of a mean-line model developed in Matlab. which includes the design and performance analysis procedure suggested by Aungier (2005). Results indicate how different design choices in terms of specific speed and velocity ratio, and different working conditions in terms of expansion ratio and turbine size may affect the efficiency of single stage radial inflow turbines in ORC systems.