Six refrigerants are evaluated as low GWP replacements for R404A using different configurations, including two-stage system architectures. These refrigerants are selected according to similar characteristics to R404A, and they are the mid-term alternatives R407A and R407F, and the long-term alternatives: L40 and DR-7 (with very low GWP and low flammability), N40 and DR-33 (with low GWP and no flammability). In order to have a complete comparison range, various operating conditions are considered, covering low and medium evaporator temperatures and two levels of condensation temperatures. Configurations selected are presented and the equations used to simulate the expected performance are shown. From a given cooling capacity, volumetric flow rate and COP are compared, taking R404A as baseline. The most efficient alternatives are the low-flammable refrigerants, L40 and DR-7, and when no flammability is acceptable, N40 and DR-33 are also very good options.