The effects of Soil-Structure Interaction (SSI) on the response of coupled wall-frame structures on pile foundations are investigated. The analysis methodology based on the substructure method is re-called focusing on the modelling of pile group foundations. The iner-tial interaction analysis is performed in the time domain by using a fi-nite element model of the superstructure and suitable Lumped Pa-rameter Models (LPMs) are implemented to reproduce the frequency-dependent compliance of the soil-foundation systems. The effects of SSI are evaluated by considering realistic case studies consisting of 6-storey 4-bay wall-frame structures founded on piles. Moderate and strong seismic actions are simulated employing real and artificial earthqua...