The European building sector is responsible for approximately 40% of total energy consumption and for 36% of greenhouse gas emissions. Identifying technological solutions capable of reducing energy consumption and greenhouse gas emissions is one of the main objectives of the European Commission. Ground source heat pumps (GSHPs) are of particular interest for this purpose, promising a considerable reduction in greenhouse gas emissions of HVAC systems. This paper reports the results of the energetic analysis carried out within the EU research project GEO4CIVHIC about the performance of geothermal heat pumps working with low-GWP refrigerants as alternatives for R134a and R410A. The work has been carried out through computer simulations based on base and regenerative reverse cycles. Several heat sink and heat source temperature conditions have been considered in order to evaluate the GSHPs’ performance in the whole range of real conditions that can be found in Europe. Particular attention has been paid to the evaluation of compression isentropic efficiency and its influence on the overall cycle performance when dealing with steady-state heat pump simulations. To do so, five different scenarios of isentropic efficiency calculation have been studied and discussed.