In this work, a cascade refrigeration system operating with four different ecological refrigerant pairs was modeled. This system uses R744 (Carbon dioxide) in the low-temperature cycle and operates with R290 (propane), R1234yf (2,3,3,3-tetrafluoropropene), R152a (1,1-difluorethane), and R717 (ammonia) in the high-temperature cycle. Energetic, exergetic, environmental, and economic performance of the cascade system was investigated to determine the most appropriate ecological refrigerant couple. The parameters used in each mentioned performance were COP (Coeffcient of Performance), ɳ_exergy (Exergy Effciency), TEWI (Total Equivalent Warming Impact), ECOP (Ecological coeffcient of performance), and C_ total (Total plant cost rate), respectively. The results showed that the cascade refrigeration system operating with R744/R717 provided the best performance for the thermodynamic conditions analyzed, presenting a COP of 2.10, ɳ_exergy of 56.9%, C_ total of 24 334 USD/year, ECOP of 4.86, and TEWI of 25.67 tons of CO2. Finally, evaluating the total plant cost rate of this cascade system, it was noted that the capital and maintenance cost rate ðC_ CMÞ corresponds to 89.1% of the C_ total value, the operational cost rate ðC_ opÞ corresponds to 10.27% of the C_ total value and the environmental cost rate ðC_ envÞ corresponds to 0.63% of C_ total.