AbstractThis experimental study evaluates the energy performance and climatic changes of a cascade cooling system operating with the R134a/R744 pairs (cooling capacity of 4.5‐6 kW) and R438A/R744. In both cases, the low‐temperature refrigerant, R744, operated under subcritical conditions. The experimental apparatus basically consists of two vapor‐compression cycles coupled by a plate cascade condenser. Two operational variables, from R744 cycle, were controlled: the degree‐of‐superheat and the compressor frequency. The experiment was initially assembled to pair R134a/R744. Subsequently, the R134a refrigerant charge in the high‐temperature cycle was replaced by R438A, on a drop‐in basis. The two systems, R134a/R744 and R438A/R744, were compared for similar cooling capacities and cold chamber air temperatures. Results showed that the energy consumption of the high‐temperature compressor, operating with R438A, was higher than R134a for all tests. As a result, the COP values for R438A/R744 were 30% lower than those for R134a/R744. The greenhouse gases emissions of the two systems were evaluated using the total equivalent warming impact factor, TEWI, whose value for the R438A/R744 pair was approximately 29.5% higher, compared with R134a/R744. Since R438A was originally designed to substitute R22, a few comparative tests were carried out with the latter, always with R744 as the low‐temperature cycle working fluid.