Changes in story stiffness and natural frequency of a high-rise building on the E-defense full-scale shaking test are experimentally evaluated from small excitations to the end of the ultimate shakes, which are expected to employ as damage index for structural health monitoring. Two kinds of changes are observed similarly from both shake test and ambient vibration, which occurred in the first seismic experiences by small excitations and after the severe damage when complete ruptures on main girders appeared in ultimate shakes. The latter severe changes in story stiffness are well-simulated by using a finite element analysis for seismic design.