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Refrigeration systems are great energy consumers and in the industrial sector cycles operating with high energy efficiency contributes to guarantee commercial competitiveness. Cascade Refrigeration Systems (CRS) are an efficient alternative to the traditional vapor compression cycle (VCC), presenting versatility by allowing a combination of cycles with distinct operating principles and use of pure refrigerants or mixtures. Refrigerants with low environmental impact such as inorganic compounds, hydrocarbons, and ethers, pure or as mixtures, have gained attention of researchers as potential substitutes for harmful halogenated refrigerants. Refrigerant mixtures or alternative cycles can achieve significant gains in the CRS performance. The present work aims at the evaluation of CRS with purpose of increasing the thermodynamic performance according to two approaches: using nonazeotropic mixtures (CO 2 /Propene, CO 2 /Dimethyl Ether, CO 2 /NH 3 ) in the High an Low Temperature Cycles (HTC and LTC, respectively) and the use of alternative cycles (as Flash Tank Vapor Injection -FTVI, or Intern Heat Exchanger -IHX) as VCC substitutes. Systems were simulated in Aspen Hysys ® v. 8.4 based on a refrigeration of a secondary fluid from -5 °C to -20 ° C with a fixed refrigeration capacity of 100 kW. A parametric analysis was performed to compare the thermodynamic performance of CRS, according to energetic (COP) and exergetic analysis, to the pure refrigerants results. FTVI, IHX and VCC cycles were compared as well. Systems were optimized to determine the maximum COP setting. The presence of mixtures in both CRS cycles generated higher COPs, however, the LTC composition mixture generated the greatest impact on the performance. Benefits observed in the parametric analysis using mixtures were: lower refrigerant mass flow; less compression work; lower rate of total exergy destruction; and greater exergetic efficiency and COP. Optimization showed that the gain in COP by the use of mixtures varied from 18 to 32% in relation to the pure refrigerants. Mixture with the highest COP (2.34) was CO 2 /Dimethyl Ether using 20 wt% CO 2 in the HTC and 10 wt% CO 2 in the LTC. Comparing SRC-VCC COP (2.34) and the SRC-FTVI (2.38) small differences were observed for the operational conditions studied. Due to the low gain, greater number of equipment and complexity the use of SRC-FTVI cycle does not bring additional advantages. The SRC-IHX cycle was not optimized due to the small gains compared to the SRC-VCC in the evaluated operational conditions.