One of the most commonly refrigeration systems is the vapor compression refrigeration system. Since energy saving and environmental friendliness remain a challenge, researchers are working hard to find an effective solution to improve the performance of vapor compression refrigeration systems while committing to environmental standards. The main goal of this paper is to identify the best and closest alternative refrigerant to R22 among the alternative cooling fluids taken into consideration in terms of thermodynamic and mechanical properties, environmental protection, and safety of handling. This work presents an analysis and comparison of the various performance measures for a vapor compression refrigeration cycle operating without using and using a heat exchanger for environmentally friendly alternative refrigerants, namely R410A, R407A, R407C, R438, RS-44b, and R417A, and compares them with the refrigerant R22, which has direct environmental impacts on the ozone layer (ODP) and global warming (GWP). The computer simulation program Chemours Refrigerant Expert 1 was used to conduct the analyses. The performance parameters analyzed are coefficient of performance, compressor work, cooling capacity, temperature of condensation, intake and exhaust pressure, volumetric capacity, theoretical displacement, intake, exhaust, condensation and evaporation temperature without and with a heat exchanger, and super heating temperature with a heat exchanger. It was concluded from this study that the best alternative to R22 refrigerant among the alternative refrigerants taken into consideration in the study is the RS-44b refrigerant in terms of all performance measures and environmentally friendly. Keywords: Refrigerant; Vapor compression; Performance measures; Evaporation; Heat exchanger.