Heat production accounted in 2021 for 50 % of the energy end use globally, where a strongconnection to fossil sources still exists. Large-scale electrical heat pumps can therefore have akey role in the energy system to enable a decreased reliance on fossil fuels and at the same timecontribute to stable system when incorporating more intermittent renewable sources. To operatea heat pump, a working fluid i.e., refrigerant is required. Historically these substances havebeen ozone depleting with a significant global warming potential. Applied regulations andlegislations have therefore limited the substances possible to implement. This study therefore focuses on investigating potential future refrigerants in LSHPs, by studying both current and potential future legislations and regulations but also the potential performanceof the substances. The performance was evaluated for two operational condition cases wherethe first focused on meeting the supply and demand of a third generation district heating systemwith an evaporation temperature of 0 °C. The second case investigated a middle temperature industrial process with an evaporation temperature of 33 °C. For both cases a two-stage compressor heat pump cycle was considered. Substances available in the database REFPROP were considered, where legislations and regulations, classifications, thermodynamic properties, and the performance were investigated. Substances not fulfilling the set criterions were eliminated. Seven substances were then investigated in depth where e.g., the volume flow rate, performance, operational electricity cost and both footprint and cost of the evaporator were considered. All substances were investigated both with and without an internal liquid-suction HEX, to investigate how such component potentially could affect the performance. The result of the study shows that environmental, safety aspects and thermodynamic propertieshave a large impact on possible refrigerants, with a decrease from 160 available substances to20 possible for each case. If an evaporation pressure in the vacuum range or a transcritical cyclewould have been investigated the number of possible refrigerants would increase. Out of the 20possible substances, seven substances namely isobutane, butane, isobutene, butene, propane,perfluoropentane and isopentane were chosen for further investigation. The performance andelectrical operational cost can be concluded to be fairly similar, with an increase when includingan internal liquid-suction HEX. The performance for case 2, is although slightly higher, whereperfluoropentane performs superior. The high GWP value for perfluoropentane however limitsits possibility to be used. Lastly the size and cost of the evaporator was investigated. It couldbe concluded that case 1 required a smaller design than case 2, related to the size of the HTCvalue.