In this paper, we investigate the adoption of working-fluid mixtures in ORC systems operating in combined heat and power (CHP) mode, with a power output provided by the expanding working fluid in the ORC turbine and a thermal energy output provided by the cooling water exiting (as a hot-water supply) the ORC condenser. We present a methodology for selecting optimal working-fluids in ORC systems with optimal CHP heat-to-electricity ratio and heat-supply temperature settings to match the seasonal variation in heat demand (temperature and intermittency of the load) of different end-users. A number of representative industrial waste-heat sources are considered by varying the ORC heat-source temperature over the range 150-330 degrees C. It is found that, a higher hot-water outlet temperature increases the exergy of the heat-sink stream but decreases the power output of the expander. Conversely, a low outlet temperature (similar to 30 degrees C) allows for a high power-output, but a low cooling-stream exergy and hence a low potential to heat buildings or to cover other industrial thermal-energy demands. The results demonstrate that the optimal ORC shaft-power outputs vary considerably, from 9 MW up to 26 MW, while up to 10 MW of heating exergy is provided, with fuel savings in excess of 10%. It also emerges that single component working fluids such as n-pentane appear to be optimal for fulfilling low-temperature heat demands, while working-fluid mixtures become optimal at higher heat-demand temperatures. In particular, the working-fluid mixture of 70% n-octane +30% n-pentane results in an ORC-CHP system with the highest ORC exergy efficiency of 63% when utilizing 330 degrees C waste heat and delivering 90 degrees C hot water. The results of this research indicate that, when optimizing the global performance of ORC-CHP systems fed by industrial waste-heat sources, the temperature and load pattern of the cogenerated heat demand are crucial factors affecting the selection of the working fluid. (c) 2017 The Author(s). Published by Elsevier Ltd.