Among anti-seismic technologies, base isolation is a very effective means of mitigating damage to structural and nonstructural components, such as equipment. However, most seismic isolation systems are designed for mitigating only horizontal seismic responses because the realization of a vertical isolation system (VIS) is difficult. The difficulty is primarily due to conflicting isolation stiffness demands in the static and dynamic states for a VIS, which requires sufficient rigidity to support the self-weight of the isolated object in the static state, but sufficient flexibility to lengthen the isolation period and uncouple the ground motion in the dynamic state. To overcome this problem, a semi-active VIS, called the piezoelectric inertia-type vertical isolation system (PIVIS), is proposed in this study. PIVIS is composed of a piezoelectric friction damper (PFD) and a leverage mechanism with a counterweight. The counterweight provides an uplifting force in the static state and an extra inertial force in the dynamic state; therefore, the effective vertical stiffness of PIVIS is higher in the static state and lower in the dynamic state. The PFD provides a controllable friction force for PIVIS to further prevent its excessive displacement. For experimental verification, a shaking table test was conducted on a prototype PIVIS controlled by a simple controller. The experimental results well agree with the theoretical results. To further investigate the isolation performance of PIVIS, the seismic responses of PIVIS were simulated numerically by considering 14 vertical ground motions with different characteristics. The responses of PIVIS were compared with those of a traditional VIS and a passive system (PIVIS without control). The numerical results demonstrate that compared with the traditional and passive systems, PIVIS can effectively suppress isolation displacement in all kinds of earthquake with various peak ground accelerations and frequency content while maintaining its isolation efficiency. The proposed system is particularly effective for nearfault earthquakes with long-period components, for which it prevents resonant-like motion.