This study used wind tunnel experiments and a Computational Fluid Dynamics (CFD) model to investigate the natural ventilation in buildings with atrium. The surface pressures are measured by a pressure scanning, and the ventilation rates are measured by a tracer gas decay method. The results of laboratory experiments are used to validate the simulation of the CFD model. Then the CFD model is employed to systematically investigate the natural ventilation of atrium buildings with operable opening. The simulation results reveal that the ventilation rate of buildings with one single opening on the roof is smaller than that of buildings with two openings (one on the sidewall and another on the roof).The ventilation rate is proportional to the opening area and external wind speed. The combined effect of wind pressure and thermal buoyancy is dominated by wind-driven ventilation when wind speed is larger than 3.0 m/s. Furthermore, compared to the flat roofing, inclined roofing could enhance the wind-driven natural ventilation.