Design criteria, modeling rules, and analysis principles of seismic isolation systems have already found place in important building codes and standards such as the Uniform Building Code and ASCE/SEI 7-05. Although real behaviors of isolation systems composed of high damping or lead rubber bearings are nonlinear, equivalent linear models can be obtained using effective stiffness and damping which makes use of linear seismic analysis methods for seismic-isolated buildings possible. However, equivalent linear modeling and analysis may lead to errors in seismic response terms of multi-story buildings and thus need to be assessed comprehensively. This study investigates the accuracy of equivalent linear modeling via numerical experiments conducted on generic five-story three dimensional seismic-isolated buildings. A wide range of nonlinear isolation systems with different characteristics and their equivalent linear counterparts are subjected to historical earthquakes and isolation system displacements, top floor accelerations, story drifts, base shears, and torsional base moments are compared. Relations between the accuracy of the estimates of peak structural responses from equivalent linear models and typical characteristics of nonlinear isolation systems including effective period, rigid-body mode period, effective viscous damping ratio, and post-yield to pre-yield stiffness ratio are established. Influence of biaxial interaction and plan eccentricity are also examined.