This paper discusses modeling the energy performance of an office equipped with a conventional insulated glazing unit with exterior shading and with three multiple-skin facade typologies (an airflow window, a supply air window, and a naturally ventilated window) under typical Belgian weather conditions. It is found that multiple-skin facades may improve the energy efficiency. However, the analysis shows that variants performing well in winter are not necessarily beneficial in summer. Combining typologies or changing the systems' settings according to the particular situation will be necessary to obtain an overall year-round improvement. The results further indicate that evaluating the energy efficiency of multiple-skin facades cannot be performed by solely analyzing the transmission losses and gains. It is imperative to take into account the enthalpy change of the cavity air and to perform a whole building energy analysis.