Although CO 2 as refrigerant is well known for having the lowest global warming potential (GWP), and commercial domestic heat pump water heater systems exist, its long expected wide spread use has not fully unfolded. Indeed, CO 2 poses some technological difficulties with respect to conventional refrigerants, but currently, these difficulties have been largely overcome. Numerous studies show that CO 2 heat pump water heaters can improve the coefficient of performance (COP) of conventional ones in the given conditions. In this study, the performances of transcritical CO 2 and R410A heat pump water heaters were compared for an integrated nearly zero-energy building (NZEB) application. The thermodynamic cycle of two commercial systems were modelled integrating experimental data, and these models were then used to analyse both heat pumps receiving and producing hot water at equal temperatures, operating at the same ambient temperature. Within the range of operation of the system, it is unclear which would achieve the better COP, as it depends critically on the conditions of operation, which in turn depend on the ambient conditions and especially on the actual use of the water. Technology changes on each side of the line of equal performance conditions of operation (EPOC), a useful design tool developed in the study. The transcritical CO 2 is more sensitive to operating conditions, and thus offers greater flexibility to the designer, as it allows improving performance by optimising the global system design.