The advanced exergy method provides engineers with the best information with respect to options for improving the overall thermodynamic efficiency of an energy conversion system. This paper presents the results of the advanced exergy analysis of an air source heat pump to perform a comparison involving different working fluids, i.e.R410A, R134a and some of their eco-friendlier replacements (R600a, R290, R1270, R1234ze(E)), assuming the same heat demand for the condenser and the same low temperatures for the air. It was found that the biggest exergy destruction belongs to the thermodynamic cycle with R410A. In case of applying a R410A cycle with only unavoidable irreversibilities, the total exergy destruction could be decreased by 47%. Compared to R410A additional decrease of the total exergy destruction could be obtained in case of only unavoidable irreversibilities for R600a (14.6%), R1270 (8.5%), R290 (8.5%) and R1234ze (7.9%). This reduction was found to be 10.4% for R134a. The biggest share of avoidable exergy destruction in the investigated heat pumps could be removed by reducing the irreversibilities within the evaporator. Taking into account technological limitations, in case of removing all the avoidable irreversibilities within the evaporator 26% of the total exergy destruction could be decreased in the investigated heat pump with R410A. In addition, in comparison with the R410A cycle, additional decrease of the total exergy destruction could be obtained in case of reducing irreversibilities within only the evaporator and replacing R410A with R600a (13.1%), R1270 (7.9%), R290 (7.5%) and R1234ze(E) (7.5%). This reduction was found to be 9.6% for R134a. Therefore, it could be concluded that today’s most powerful thermodynamic tool, i.e. the advanced exergy analysis, suggests the adoption of hydrocarbons in air-source heat pump units over R1234ze(E) as replacements of currently used working fluids (i.e. R410A and R134a).