The paper explores the seismic performance of reinforced concrete (RC) frames infilled with deformable masonry panels incorporating horizontal sliding joints. These innovative infill systems are designed to overcome the seismic vulnerabilities observed in traditional RC structures with rigid infills, where the interaction between the frame and infill often leads to undesirable brittle failure modes. The study analyses the response of different layouts of a 5-storey and a 7-storey structures, adopted as RC case studies, varying the infill properties and layouts and the design ductility classes. The structural responses are assessed through linear, non-linear static and non-linear dynamic analyses are discussed across different seismic performance limit states. Focus is on the ductility verification, collapse mechanisms, behaviour factors and non-regularity in the infill distribution. Comparative results reveal how the presence of deformable infills, varying significant design parameters and different modelling strategies, affects the global seismic response and they provide support to the development of design guidelines. Overall, the findings confirm the effectiveness of sliding-joint infills in improving seismic performance and support their possible incorporation into performance-based design methodologies. The study also highlights the potential capability of Response Spectrum Analysis and Pushover analysis to capture the seismic demands in infilled frames.