base isolation can significantly improve the seismic performance of structures. However, significant 3D movement coupling and rocking behavior of the superstructure due to the high gravity center of the structure can be observed, which will lead to a complex design of the isolation system and the isolators. In addition, as the 3D isolators are installed beneath the structures, they need to support the heavy weight of the superstructure with low vertical stiffness. It is difficult to meet both the vertical load and stiffness design demands of the isolators using traditional isolation materials and mechanisms, especially for large-size structures. A separated 3D isolation scheme is proposed by installing the horizontal isolation at the base of the superstructure and the vertical isolation under the floor slabs. Simulations are carried out to examine the dynamic responses including the acceleration, inter-storey drift, and stress of structural members of a typical steel frame structure with the separated 3D isolation scheme. The isolation effect was also studied by shaking table tests of a two-storey steel frame structure.