The key to improving the efficiency of carbon dioxide (CO2) transcritical refrigeration systems is to select an appropriate two-stage compression system. In this study, the thermodynamic performance of six different CO2 transcritical two-stage refrigeration systems with expanders is compared. The design parameters are analysed to determine their respective impacts on the system coefficient of performance (COP) in order to ascertain which system configuration produces the maximum system COP. It is concluded that the system with a two-stage expander and incomplete intercooling has great advantages in terms of performance and equipment selection for the high-pressure stage in certain circumstances. Under the given conditions, the design parameters including the evaporating temperature, the condensing temperature, the compressor efficiency of the high-pressure stage, and the compressor efficiency of the low-pressure stage impact on the system performance. It should be noted that the gas cooler outlet temperature and the compressor efficiency of the low-pressure stage are the major factors which affect the efficiency of the system; thus, the system design and equipment selection should minimise the gas cooler outlet temperature and select a high-efficiency compressor for the low-pressure stage to ensure efficient and safe operation.