In this paper a comparative study of different configurations of refrigeration systems is presented. The main focus of the study is the comparison of energy efficiency and TEWI. The study was done by means of simulation software. According to the study a suitable system configuration with natural refrigerants not only reduces the direct global warming impact, but also improves energy efficiency. The study indicates that in comparison to two independent R404A systems for supermarket applications, an NH3/CO2 cascade system will always have superior performance, while a CO2 booster system provides best efficiency in moderate and cold climates. A R290/CO2 cascade has similar performance to the reference system (heatreclaimed not considered). Even though real system data are scarce, available studies confirm the theoretical simulations.