The increasing demand for energy-efficient buildings has driven the development of innovative renovation concepts, such as the I-DIFFER system, which integrates Double Skin Facades (DSF) with Diffuse Ceiling Ventilation (DCV). This system has demonstrated comparable or improved energy performance compared to traditional renovation approaches while ensuring a good indoor environment. The efficient implementation of I-DIFFER requires a configuration for each specific building, ideally supported by Building Performance Simulation (BPS) tools. Despite their potential, BPS tools face challenges in accurately modeling DSF and DCV due to limitations in simulating specific physical processes occurring within these systems. Furthermore, the lack of studies validating DCV models in BPS tools with empirical data raises questions about their reliability for configuring and optimizing combined systems such as I-DIFFER. This study aims to experimentally validate two BPS models, evaluating their respective capabilities in assessing the performance of the I-DIFFER system in two operational modes: cooling mode, where airflow in the DSF is driven by natural forces and mechanically driven in the DCV plenum, and heating mode, where airflow in both the DSF and DCV is mechanically driven. The experimental data is obtained from a full-scale experimental set-up, and the simulation results show that both models are sufficiently accurate for predicting thermal conditions in the room with the I-DIFFER system. However, both models show weaknesses in predicting peak-hour thermal performance and face challenges in accurately simulating heat transfer between the DCV plenum and the room, potentially limiting the development of optimal control strategies.