In order to investigate the effect of aerodynamic interaction between vehicles and a bridge on the driving safety of vehicles on a bridge, the Taihong Yangtze River Bridge of Chongqing in China was taken as an example, and the driving safety of vehicles and dynamic responses of vehicles and the bridge under strong wind were investigated for the two typical types of vehicles——a van and a car. Firstly, based on the wind-vehicle-bridge coupling analysis system, the vertical, pitching and rolling accelerations of the vehicles, and the lateral acceleration of the bridge were calculated with and without consideration of the aerodynamic interference between the vehicles and bridge. Then, these acceleration responses of the vehicles and bridge were applied to the local accident analysis program built by MATLAB. The sideslip displacement and the reaction force ratio of each wheel of the vehicles were calculated. The accidents of the vehicles were assessed by comparing the calculated responses of the vehicles with the accident criteria. Further, the accident critical wind speeds of the vehicles at different traveling speeds were obtained by gradually increasing the traveling speed and wind speed, and the curves of the accident critical wind speed versus the traveling speed for the two types of vehicles with and without consideration of the aerodynamic interference were plotted. The results show that the aerodynamic interference between the vehicles and the bridge has a significant influence on the driving safety of vehicles on the bridge. The assess results are relatively conservative if the aerodynamic interference between the vehicles and bridge is not considered. In addition, the aerodynamic interference also affects the vehicle accident type. This paper can provide a reasonable theoretical reference and data support for the operation safety and scientific management of long-span bridges under strong wind weather conditions.