In both, newly built and renovated buildings the building air-tightness has to be ensured. With a tight building envelope comes a low infiltration air-exchange. A minimum outdoor air exchange to ensure acceptable moisture and indoor air quality levels must be maintained. A model is introduced, that couples hygrothermal whole building simulation with a multi-zone air-flow simulation. This coupling allows assessing the combined effects of air-flow on building energy use, comfort conditions, air quality and possible hygric issues. An application example shows the use of the software for a low rise residential building. In a first step the parameterization of the air-flow network is checked by computing the resulting infiltration air-flow with closed windows. The maximum achievable natural air exchange for different window types and openings, like pivot-hung windows, windows opened with a small parallel gap around and side-hung windows is assessed. Based on these numbers it is assessed if any of the above mentioned opening options alone with a certain opening duration is able to achieve good indoor air quality and acceptable indoor moisture levels to avoid any hygric problems or if a combination of some of the measures is required. The presented dynamic hygrothermal whole building simulation coupled with a multi-zone air-flow model is capable of simulating the effects of different window opening options and strategies on building energy demand, indoor comfort conditions and air quality and on the hygrothermal building component performance. It is shown, that a sufficient air exchange can be realized even with a parallel-action window with small opening gaps which can be run with motor drives. Especially demand controlled opening strategies can be developed that ensure high indoor air quality and comfort conditions while also controlling humidity indoors to avoid moisture damage. Also an improvement for summer conditions can be achieved by ventilative cooling with this type of window opening.