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The indirect consequences of a strong seismic event in a metropolitan motorway (such as the deterioration of its serviceability) can be effectively mitigated through timely development and implementation of a rapid response system. The development of such a system requires knowledge of the seismic vulnerability of critical infrastructures, such as bridges. However, a typical motorway network is composed of a multitude of bridges, making it practically impossible to analyse each case in full detail as the amount of computational effort would be overly excessive. Hence, there is a need to develop adequately simplified nut realistic models, which is the scope of the present paper. In order to develop such models, the effect of each structural component is examined, with emphasis on soil-structure interaction (SSI). For this purpose a detailed three-dimensional numerical model is developed, utilizing an overpass bridge from the Attica Motorway in Athens (Greece) as an illustrative example. The seismic performance of the bridge is studied applying 29 real seismic records of different intensities and kinematic characteristics in the transverse and the longitudinal direction. A simplified model is developed, consisting of a single pier carrying an appropriate mass, and connected with a series of springs and dashpots representing the deck and the seismic isolation system. SSI is taken into account in a similar manner, replacing the foundation and the soil with equivalent springs and dashpots.