In this study, TOPSIS analysis was applied to decide the optimum refrigerants with cost, safety, environmental and enviroeconomic concerns along with thermophysical properties. A vapor compression refrigeration cycle performance was investigated with the statistical and thermodynamic approaches. COP, exergy efficiency, total, avoidable, and unavoidable exergy destruction rates were calculated for various experimental designs. According to the relative proximity to the ideal solution, the best refrigerants for the system were determined as R513a, R134a, and R448a, respectively. The optimum parameters for the greatest COP and exergetic performance were calculated as A(2)B(3)C(1)D(3)E(3)F(1). In the optimum case, the best COP and exergy efficiency of 2.65 and 10% and the lowest total exergy destruction of 0.34 kW were achieved for R134a. These are larger than all other 27 experimental patterns. The parameters having an impact on the COP, exergy efficiency, and total exergy destruction rate were found as T-EVA > T-CON > Refrigerant > eta(COM,H) > eta(COM,L) > P-in (B > C > A > E > D > F). The evaporator temperature is the most effective parameter on the performance with about 42.8% for the performance. It is followed by that of condenser and refrigerant to be 32.5% and 13.8%. The most effective parameters for the avoidable exergy destruction rate were high-and low-pressure compressors efficiencies, evaporator temperature, and condenser temperature, respectively.