Natural ventilation of buildings refers to the replacement of indoor air with outdoor air due to pressure differences caused by wind and/or buoyancy. It is often expressed in terms of the air change rate per hour (ACH). The pressure differences created by the wind depend – among others – on the wind speed, the wind direction, the configuration of surrounding buildings and the surrounding topography. Computational Fluid Dynamics (CFD) has been used extensively in natural ventilation research. However, most CFD studies were performed for only a limited number of wind directions and/or without considering the urban surroundings. This paper presents isothermal CFD simulations of coupled urban wind flow and indoor natural ventilation to assess the influence of wind direction and urban surroundings on the ACH of a large semi-enclosed stadium. Simulations are performed for eight wind directions and for a computational model with and without the surrounding buildings. CFD solution verification is conducted by performing a grid-sensitivity analysis. CFD validation is performed with on-site wind velocity measurements. The simulated differences in ACH between wind directions can go up to 75% (without surrounding buildings) and 152% (with surrounding buildings). Furthermore, comparing the simulations with and without surrounding buildings showed that neglecting the surroundings can lead to overestimations of the ACH with up to 96%.