A systematic approach has been developed for fast evaluation of large sets of fluids and mixtures for power generation using ORC (Organic Rankine Cycle) to identify the best refrigerants with low GWP (global warming potentials). A model has been created to calculate performance of a basic cycle for pure fluids as well as mixtures based on heat balance and pinch point analysis using the property package of RefProp 9.0. Processes in both heat exchangers and turbine are discretized to compute key design and operating parameters. With any given resource temperature, cycle performance are optimized on both heating and cooling sides of the cycle for maximum power generation or maximum efficiency. Case studies have been performed for analysis of fluids pre-screened with EHS (environment, health and safety) criteria, including toxicity, ODP (ozone depletion potential) and GWP. Major design and operating constraints have been evaluated through simulation and applied for fluid selection, such as dry expansion in turbine. Candidate pure fluids and binary mixtures with low GWP and high performance have been identified at different resource temperatures for further detailed design evaluation. This approach has been demonstrated for efficient evaluation of large sets of pure fluids and mixtures for any given resource temperature. (C) 2015 Elsevier Ltd. All rights reserved.