This paper reports a study on the Intermediate Isolation System (IIS) applied to existing buildings. This kind of application is particularly suitable when a vertical addition is planned for buildings in seismic zones; in such a case, an isolation system can be placed at the base of the extension to prevent the increase, or, better, to reduce the seismic demand on the existing structure. In previous works, parametric response spectrum analyses have been carried out on lumped mass models by varying the period of the isolation system. As a result, a sort of IIS design spectrum has been derived and used for selecting design solutions for the vertical extension that minimize the overall seismic response. In this paper, the above design indications are assessed in the light of nonlinear time history analyses, accounting for the hysteretic response of the existing structure and the nonlinear behaviour of the isolation system. The IIS configurations are analysed and the results are discussed and compared in terms of peak response. In light of the obtained analysis results, the effectiveness and robustness of IIS applications for vertical extensions are discussed, and design implications are suggested.