This paper examines how the decision to include (or exclude) masonry infill walls in the modelling of non-seismically designed RC framed structures can affect the results of the EC8-3 seismic assessment process. A frequently used macro-modelling technique for the simulation of infill panels within bounding RC members is first reviewed. A case-study application follows in which the seismic assessment of a sample structure is carried out, with and without considering the effect of its infill walls, using nonlinear static and dynamic analysis models. The obtained results are then discussed according to the applicable limit states’ performance requirements, and conclusions are drawn regarding the overall outcome. The study indicates that, when low and medium seismic input motions constitute the base demand for the assessment of older-type RC framed buildings, the protection provided to the RC members by the confined masonry infill panels should not be neglected. Moreover, it shows that the identification of the most likely collapse mechanism might also be significantly influenced by the modelling decision in question. As such, the default recommendation is to include masonry infill walls in the modelling of such structures.