The interest in natural refrigerants, such as carbon dioxide, has been growing in recent years due to the high direct global warming potential of common HFC refrigerants. Despite the environment-friendly characteristics of CO2 as a refrigerant, due to high heat rejection temperatures and transcritical operation, CO2 cannot match the high energy efficiency associated with current HFC technology. Thus, additional measures must be taken to achieve high COP when using CO2. One approach is to use CO2 as one of the fluids in a cascade system along with a HFC refrigerant as the high side fluid. Such systems may have roughly 75% less HFC refrigerant charge, and the global warming potential is reduced compared to a baseline system using only HFC refrigerant. When used as a second fluid in a cascade system, the CO2 cycle remains in the subcritical region, thus increasing the cycle’s COP. In this paper an approach to model cascade systems is presented. The model is validated using experimental data for a R404A/CO2 cascade system and results are discussed. The simulation tool is developed to account for additional components in the system such as multiple condensers and compressors. Some test points in the experimental system were run using a set of parallel compressors, which can be easily addressed by the simulation tool.