Abstract: In order to research the coupled vibration effects when a train runs through a long-span twin tower steel truss cable-stayed bridge at a high speed to provide a reference for the design of the same type of bridges, a numerical simulation model for coupled vibration was set up by taking Yujiang River bridge, a long-span steel truss cable-stayed bridge, on Nanning-Guangzhou high-speed railway as a study object. A dynamic analysis model for the bridge was established with the finite element software ANSYS, and its natural vibration properties were analyzed. A spatial dynamic model for German ICE3 train was set up by the multi-system dynamics software SIMPACK. The spatial coupled vibration responses of a vehicle-bridge system under the conditions of different strain speeds were calculated by co-simulation based on the SIMPACK and the ANSYS. The results show that when a strain runs respectively at a speed of 250, 270, 290 or 300 km/h, all its safety indexes can meet standard requirements, Sperling comfort indexes of motor car and trailer both are less than 2.5. The maximum vertical and lateral deflection-span ratios are respectively 1/1 843 and 1/83 000, the maximum vertical and lateral accelerations are 0.386 and 0.107 m/s2, respectively, and the maximum impact coefficient is 1.200. All these indexes show that the bridge has a sufficient rigidity, and its vibration is in good condition.