The air change rate (ACR) of naturally ventilated dairy buildings (NVDBs) plays an important part in the design and control of the ventilation system, as wel as in the estimation of the gaseous emission rate. The objectives of this research were to model theACR based on a quantitative investigation of the relationship between theACR and its potential influencing factors, including the opening ratio (r), the building length to width ratio (α), the wind speed (U), and the wind direction (θ). The investigations were performed using the response surface methodology integrated with the Box-Behnken design and Computational Fluid Dynamics (CFD) simulations. Three response surface models of theACR of NVDBs were established for three opening ratio ranges of 5％–42.5％, 42.5％–80％, and 5％–80％, respectively. It was found that the selection of the opening ratio range had almost no effect on the developed response surface models. The results showed that theACR of NVDBs was not influenced byα, but was significantly affected byr,U,θ, and interaction effects between every two of the three factors. The highestACR was 6.7 s?1, 6.0 s?1, and 4.0 s?1 whenθ,U, andr was at their respective medium value while the rest parameters were at the highest values, indicating that ther played an important role in the value ofACR. It was concluded that in the prediction of theACR of a building, the influences of both individual and interactional effects ofθ,U, andr should be considered.