Rollover of high-sided vehicles represents a serious concern for running safety, especially when they run on exposed sites such as viaducts and bridges. In particular, the present paper investigates the interaction between a tractor semitrailer combination and the wake of a tower bridge in cross wind conditions. The proposed methodology is based on a multi-body vehicle model coupled with a force distribution approach to calculate the aerodynamic forces acting on the vehicle during the tower wake crossing, which relies on static vehicle CFD simulations/wind tunnel tests. To asses reliability of the developed methodology, obtained results are compared with moving vehicle CFD simulations (based on a moving mesh approach). Numerical results state that the developed model may represent a valuable tool for investigating wind-shielding solutions at the design stage of bridges. The developed model in fact provides results in good agreement with moving vehicle CFD data, but allows to significantly reduce computation effort and the coupling with a driver model.