In selecting the type of foundation best suited for mid-rise buildings in high risk seismic zones, design engineers may consider that a shallow foundation, a pile foundation, or a pile-raft foundation can best carry the static and dynamic loads. However, di®erent types of foundations behave di®erently during earthquakes, depending on the soil-structure interaction (SSI) where the properties of the in situ soil and type of foundation change the dynamic characteristics (natural frequency and damping) of the soil-foundation-structure system. In order to investigate the di®erent characteristics of SSI and its in°uence on the seismic response of building frames, a 3D numerical model of a 15-storey full-scale (prototype) structure was simulated with four di®erent types of foundations: (i) A¯xed-based structure that excludes the SSI, (ii) a structure supported by a shallow foundation, (iii) a structure supported by a pile-raft foundation in soft soil and (iv) a structure supported by a°oating (frictional) pile foundation in soft soil. Finite di®erence analyzes with FLAC3D were then conducted using real earthquake records that incorporated material (soil and superstructure) and geometric (uplifting, gapping and P À Á e®ects) nonlinearities. The 3D numerical modeling procedure had previously been veri¯ed against experimental shaking table tests conducted by the authors. The results are then presented and compared in terms of soil ampli¯cation, shear force distribution and rocking of the superstructure, including its lateral deformation and drift. The results showed that the type of foundation is a major contributor to the seismic response of buildings with SSI and should therefore be given careful consideration in order to ensure a safe and cost e®ective design.