Studies have found that the CEN and NFRC methods produce different U-values for the same window. A comparative evaluation of the NFRC and CEN U-value calculation methods was conducted for North American residential high performance window products, as well as several parameters that are most influential in determining the whole window U-value for high performance windows, when utilizing different assumptions and boundary conditions, in North America’s eight climate zones. Using 2-D simulation software, THERM and WINDOW, four North American high performance frame types with double, triple and quad glazing combinations, were simulated and calculated according to the NFRC and CEN standard methods. Overall, the trend showed that for the specific window combinations of this study, the higher the performance of the IGU, the lesser the differences in the whole window U-value of both methods. Several strategies were proposed to support the possibility of the harmonization of both calculation methods.