Building energy simulation (BES) and Airflow network (AFN) programs generally incorporate wind pressure coefficients (Cp) estimated from secondary sources, namely data bases or analytical models. As these coefficients are influenced by a wide range of parameters, it is difficult to obtain reliable Cp data. This leads to uncertainties in BES-AFN models results, especially for naturally ventilated building studies, where air change rate which strongly depends on Cp, is a key value for thermal comfort and energy consumption results. This study focuses on naturally ventilated buildings in tropical climate and presents an alternative approach to estimate wind pressure coefficient. Computational fluid dynamics (CFD) simulations are performed to calculate wind-driven airflow rates at building opening level. Then wind pressure coefficient difference ΔCp is calculated from large opening equation to be used as input data in BES-AFN program. Numerical simulations are performed for various wind directions on a typical cross-ventilated isolated building and a more complex building with opposite large openings. CFD results of wind pressure coefficient difference and airflow rate are compared to those obtained from AFN model using two different Cp sources. The results show that the calculated values vary greatly depending on the method used and highlight that an accurate estimation of wind pressure coefficient is a key parameter for evaluating natural ventilation in buildings.