A theoretical performance analysis based on the exergetic performance coefficient (EPC) criterion has been carried out for a cascade refrigeration system for different refrigerant couples. The EPC criterion is defined as the ratio of exergy output to the total exergy destruction rate (or loss rate of availability). According to the results of the study, the refrigerant couples R23-R717 show the best performance in terms of EPC and coefficient of performance from among the other refrigerant couples (R23-R290, R23-R404A, R23-R507A and R23-R717). In the analysis, R23 was used for the lower temperature cycle and the other refrigerants are used for the higher temperature cycle. The effects of the temperature difference in the cascade condenser and the evaporator and condenser temperature on the EPC, coefficient of performance and exergy destructions have been thoroughly investigated for the refrigerant couple R23-R717.