Abstract This work evaluates the thermodynamic performance of three different mixed refrigerants: R744/R1270, R744/R717 and R744/RE170 in a cascade refrigeration system composed of two vapor compression cycles. Mixture composition and condensation temperature of the cascade heat exchanger were used as inputs in a parametric analysis, while outputs considered were: compressor power, refrigerant mass flow rate in both cycles, exergy destruction rate, exergetic efficiency and coefficient of performance. Systems were optimized for COP maximization, considering a fixed cooling rate of 100 kW in the evaporator. After optimization, COP increased from 18% to 32% when compared to the values obtained for pure refrigerants. R744/RE170 mixture showed the best results with a COP of 2.34, increasing exergetic efficiency up to 30% and reducing refrigerant mass flow rate in the range from 6% to 34%, compressor power between 20% to 23% and exergy destruction rate was decreased around 31% to 36%.