This work presents an experimental analysis of a non-flammable R1234ze(E)/R134a mixture (R450A) as R134a drop-in replacement. While R134a has a high GWP value (1430), the R450A GWP is only 547. The experimental tests are carried out in a vapour compression plant equipped with a variable-speed compressor. The replacement suitability has been studied combining different operating conditions: evaporation temperature, condensation temperature and the use of an internal heat exchanger (IHX). The drop-in cooling capacity of R450A compared with R134a is 6% lower as average. R450A COP is even higher to those resulting with R134a (approximately 1%). The discharge temperature of R450A is lower than that of R134a, 2K as average. The IHX has a similar positive influence on the energy performance of both fluids. In conclusion, R450A can be considered as a good candidate to replace R134a.