The effectiveness of using digital simulations in the hospital field has been demonstrated in the design of facilities and staff training. Models such as BIM+VR [1] show how parametric design enables rapid updates and optimizations of structures using virtual reality environments. Through mockups of real hospitals, disasters have been simulated to prepare staff for such events, significantly improving the understanding of procedures to be implemented and the engagement of participants. Another critical issue of the hospital environment is the exposure of patients, staff, and the public to infectious agents due to a healthcare system failure (e.g. ventilation, water or decontamination incidents) or the wrong design and use of the clean/dirty pathways to prevent cross-contamination. Considering the latter aspect, introducing virtual reality mockups in the planning and management of clean/dirty pathways can help reduce contamination risks through the optimized design of spaces and operational flows from different perspectives (patients, staff, and the public). This article describes the construction method of the virtual mockups and the preliminary experiment results, providing evidence of VR’s potential to enhance understanding and adherence to best practices in operational procedures within healthcare facilities. The experiment involved participants who were asked to walk through a clean/dirty pathway, having different characteristics, later comparing their behavior (errors and crossing time) through scenarios that simulate typical operational conditions encountered by healthcare workers. The preliminary results show that horizontal signage significantly reduces the time patients take to reach different hospital areas compared to vertical signage (p < 0.028).