The achievement of economical designs of organic Rankine cycle (ORC) systems for deployment in a variety of applications can be greatly facilitated by computer-aided molecular design (CAMD) techniques, which require accurate and reliable group contribution (GC) equations of state (EoS) to predict the thermodynamic and transport properties of suitable and optimal working fluids. In this work, the capabilities of SAFT-γ Mie, a GC EoS, is extended to include functional groups such as −CF3 and >CF2, that can allow the design of environmentally-friendly refrigerant working fluids. The parameters of these groups in the SAFT-γ Mie EoS are regressed from experimental data. With these parameters, maximum average absolute deviations (AADs) from experimental data of 5 % for the vapour pressure, 3 % for the saturated liquid density and 3 % for the liquid-phase density are reported, confirming the suitability of this EoS for working-fluid thermodynamic property predictions. Furthermore, by employing suitable GC methods, important transport properties such as the thermal conductivity, liquid viscosity and vapour viscosity are predicted with AADs of 28 %, 23 % and 6 %, respectively. The new GC parameters are implemented in an existing CAMD-ORC model and parametric optimization studies are performed. For a relatively low-temperature (150 °C) heat source, the employment of refrigerant heptafluorobutane results in a net power output of 43 kW, which outperforms the best performing hydrocarbon (n-propane, 35 kW). This confirms the need to include refrigerants within such ORC frameworks in addition to hydrocarbons. At higher heat-source temperatures of 250 °C and 350 °C, the optimal working fluids are 2-pentene and 2-hexene, with corresponding maximum power outputs of 137 kW and 219 kW.