Decoupled infills have been recently proposed to improve the seismic performance of infilled RC frame buildings. In this paper, the so-called INODIS system, developed at the RWTH Aachen University, is investigated. The INODIS system exploits soft elastomeric material to decouple masonry infills from the surrounding frame, while withstanding OOP loads through a suitable mechanism. A typical 6-storey RC frame building equipped with, alternatively, traditional and decoupled infills is examined through Nonlinear response-time history analyses, considering IP/OOP interaction for the infills. The results of this study clearly confirm the good seismic performance and significant damage reduction achievable with decoupled infills.