Studies have found that the European Committee for Standardization (CEN) and National Fenestration Rating Council (NFRC) methods produce different U-values for the same window resulting in confusion when comparing products. A comparative evaluation of the NFRC and CEN U-value calculation methods was conducted for North American residential high-performance window products with focus on the most influential parameters in determining the whole window U-value for high-performance windows. Using two-dimensional conduction simulation software, 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 insulated glazing unit (IGU), the lesser the differences in the whole window U-value of both methods. The results showed an overall difference of 1 to 11% in whole window U-value when using the NFRC and CEN standards, lower than other studies. Generally, the NFRC standard resulted in the lower U-value for each case. Recommendations for harmonization of the two standards include aligning boundary conditions, frame cavity models, and material conductivities.