Abstract: For long-span bridges located in mountainous canyon areas, the longitudinal distributions of the incoming wind velocities along the bridge are often quite different. This non-homogeneous characteristics of the wind field makes the wind loads acting on different points of the bridge more complicated. Compared with a homogeneous wind field with constant average wind speed, the non-homogeneous wind field may pose a more severe threat to the safety of vehicles running on the bridge. To explore how the non-homogeneous wind field affects the driving safety of vehicles on bridges. A non-uniform wind field is generated with the help of a spatial wind speed distribution model and the harmonic wave superimposing method for fluctuating winds. Taking a long-span arch bridge as the engineering case study, a multibody vehicle dynamics model is developed in SIMPACK. Based on the finite element models of the flexible track and bridge structures, a dynamic model of the wind-vehicle-track-bridge system is established using the rigid-flexible coupling approach. Considering the inhomogeneity caused by the wind field position relative to the bridge span and the change in wind field range, the dynamic response characteristics of both the train and the bridge under different wind speeds and train speeds are analyzed. Results indicate that the non-homogeneous distribution of wind field has a considerable impact on the dynamic response of bridges and vehicles. The wheel unloading rate and the derailment coefficient of the train could be affected by the inhomogeneity of wind field. Under unfavorable conditions with a non-homogeneous wind field, when the vehicle is running at 100 km/h in a 25 m/s wind environment, the wheel unloading rate is likely to exceed the safety limit.