The application of the Organic Rankine Cycle to high temperature heat sources is investigated on the case study of waste heat recovery from a selected biogas plant. Two different modes of operation are distinguished: pure electric power and combined heat and power generation. The siloxanes hexamethyldisiloxane (MM) and octamethyltrisiloxane (MDM) are chosen as working fluids. Moreover, the effect of using mixtures of these components is analysed. Regarding pure electricity generation, process simulations using the simulation tool Aspen Plus show an increase in second law efficiency of 1.3% in case of 97/03 wt % MM/MDM-mixture, whereas for the combined heat and power mode a 60/40 wt % MM/MDM-mixture yields the highest efficiency with an increase of nearly 3% compared to most efficient pure fluid. Next to thermodynamic analysis, measurements of heat transfer coefficients of these siloxanes as well as their mixtures are conducted and Kandlikar’s correlation is chosen to describe the results. Based on that, heat exchanger areas for preheater and evaporator are calculated in order to check whether the poorer heat transfer characteristics of mixtures devalue their efficiency benefit due to increased heat transfer areas. Results show higher heat transfer areas of 0.9% and 14%, respectively, compared to MM.