In this study a computational model developed in Abaqus, validated through experimental testing, is employed to evaluate the performance of CLT infill panels in reinforced concrete (RC) frames, comparing them with traditional masonry. A range of configurations is analysed, including infills with and without openings. The objective of the study is to assess the advantages of CLT panels in terms of structural performance, weight, sustainability, and construction time. Research indicates that CLT infills generally enhance the lateral response of RC frames, offering higher stiffness, strength, and energy dissipation compared to masonry. The utilisation of lightweight materials in these structures serves to mitigate seismic forces, while the prefabrication process facilitates expedited construction. Furthermore, CLT offers considerable sustainability benefits due to its reduced carbon footprint and natural capacity to retain carbon absorbed during tree growth. The present study considers the impact of openings in CLT panels on their structural behaviour, providing a comprehensive comparison against traditional cladding solutions. The objective of the present study is to contribute to the broader adoption of CLT as an innovative and sustainable material for retrofitting and new construction.