In the European Union (EU), buildings are responsible for about 40% of the total final energy consumption, and 36% of the European global CO2 emissions. The European Commission released directives to push for the enhancement of the buildings energy performance and identified, beside the retrofit of the current building stock, Heating, Ventilation, and Air Conditioning (HVAC) systems as the other main way to increase renewable energy sharing and overall building energy efficiency. For this purpose, Ground Source Heat Pumps (GSHPs) represent one of the most interesting technologies to provide energy for heating, cooling, and domestic water production in residential applications, ensuring a significant reduction (e.g., up to 44% compared with air-source heat pumps) of energy consumption and the corresponding emissions. At present, GSHPs mainly employ the refrigerant R410A as the working fluid, which has a Global Warming Potential (GWP) of 2087. However, following the EU Regulation No. 517/2014 on fluorinated greenhouse gases, this high GWP refrigerant will have to be substituted for residential applications in the next years. Thus, to increase the sustainability of GSHPs, it is necessary to identify short time alternative fluids with lower GWP, before finding medium-long term solutions characterized by very low GWP. This is one of the tasks of the UE project "Most Easy, Efficient, and Low-Cost Geothermal Systems for Retrofitting Civil and Historical Buildings" (acronym GEO4CIVHIC). Here, a thorough thermodynamic analysis, based on both energy and exergy analysis, will be presented to perform a comparison between different fluids as substitutes for R410A, considered as the benchmark for GSHP applications. These fluids have been selected considering their lower flammability with respect to hydrocarbons (mainly R290), that is one of the main concerns for the companies. A parametric analysis has been performed, for a reversible GSHP cycle, at various heat source and sink conditions, with the aim to identify the fluid giving the best energetic performance and to evaluate the distribution of the irreversibilities along the cycle. Considering all these factors, R454B turned out to be the most suitable fluid to use in a ground source heat pump, working at given conditions. Special attention has been paid to the compression phase and the heat transfer in evaporator and condenser.