As a result of the technological developments, there have been significant improvements in terms of refrigeration. Due to those developments, refrigeration applications have become widespread. Refrigeration applications are used in wide range as from local applications to industrial applications. Refrigeration has also become very important especially in the area of food and health. This study deals with energy and irreversibility analysis of a two stage vapor compression refrigeration system employing various refrigerants. A computer code is developed for this purpose by using the software program (EES) which is widely used in the analysis of thermal systems. Also it has been assumed that superheating and subcooling are present in the system and the calculations has been made accordingly. Irreversibility occurring in the elements of the vapor-compression refrigeration system has been examined according to the isentropic efficiencies of the compressors. A comparison has been investigated for the selected refrigerants in terms of their irreversibilities. The minimum amount of irreversibility was obtained by using R141b in the elements, namely condenser, compressor I, compressor II, evaporator and expansion valve for both isentropic efficiency compressor I and II cases.