Power generation systems recovering waste heat, such as Organic Rankine Cycles (ORC), cannot work efficiently when the highest temperature ranges between 100 °C and 85 °C. For this reason, upgrading and recycling the low-grade waste heat is very interesting in this temperature range. High temperature heat pumps can upgrade the waste heat raising the temperature up to 150 °C, which is adequate for some productive process in the food, paper, chemical and tobacco industries. Despite the intense research effort, even focusing solely on the vapour compression heat pumps, selecting the most suitable working fluid for these applications is not trivial. The selection of a fluid for a high temperature heat pump is limited by several technical constraints and a trade-of between a high efficiency and a large volume flow rate is necessary. Since the recommended fluid may change for different combinations of heat source and heat sink temperatures, a systematic investigation of the heat pump performance with different fluids working at different operational conditions has been carried out. The effect of different technical limitations has been discussed, and the most suited fluids both with respect to the highest efficiency and optimal volume flow rate have been recommended.