Base isolation system is generally used for low-rise buildings. For high-rise buildings subjected to earthquake loads, a mid-story isolation system was proposed and applied to practical engineering. In this study, seismic responses of high-rise buildings considering the installation story of the mid-story isolation system were evaluated. To do this, the 20-story and 30-story building were used as example structures. Historical earthquakes such as Kobe (1995), Northridge (1994) and Loma Prieta (1989) earthquakes were employed applied as earthquake excitations. The installation location of the mid-story isolation system was changed from the bottom of the 1^st floor to the bottom of the top floor. The seismic responses of the example building were investigated by changing the location of the isolation layer. Based on the analytical results, when the seismic isolation system is applied, story drift ratio and acceleration response are reduced compared to the case without the isolation system. When the isolation layer is located on the lower part of the building, it is most effective. However, in that case, the possibility that the structure is unstable increases. Therefore, an engineer should consider both structural efficiency and safety when a mid-story isolation system for a high-rise building is designed.