In this study, first and second law analysis of vapor compression refrigeration cycle with two-stage and intercooler using refrigerants R134a, R404a, R407c, R410a, R507 which do not damage to ozone layer is carried out. The coefficient of performance (COP), exergetic efficiency (eta(ex)) and total irreversibility rate of the system in the different operating conditions for these refrigerants has been investigated. COP, exergetic efficiency and total irreversibility rate comparisons between refrigerants were performed. The results indicate that COP and exergetic efficiency of refrigeration system with two-stage using R134a is better than system using other refrigerants. The irreversibility rate in the system using R507 is highest.