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Heat stress and disease outbreak result in significant losses in large-scale egg productions. New ventilation systems are needed for large-scale layer production facilities to provide safe and uniform indoor environment, especially in the changing climate of global warming. This study developed a new ventilation system, upward airflow displacement ventilation (UADV) system, which allows fresh air to enter a layer house through air ducts located at the bottom of the cages, move upward by thermal buoyancy caused by hens and static pressure differences caused by exhaust fans, and ultimately exit the house through the fans installed on the roof. The performance of the UADV system was evaluated in comparison with a typical tunnel ventilation (TV) system in terms of air-exchange effectiveness, thermal environment, and airborne pathogen dispersal in both summer and winter using a validated Computational Fluid Dynamics (CFD) model. The results showed that the UADV system resulted in 46%-129% greater air-exchange effectiveness within the cages and provided a more homogeneous thermal environment with 9.4% less heat stress in summer and 68% less cold stress in winter compared with the TV system. In addition, transport of pathogens was largely inhibited in the UADV system compared with the TV system due to upward airflow and minimum air mixing across the cages. When coupled with sensible cooling of supply air, UADV system can further improve the thermal environment with a much lower ventilation rate under extremely hot and humid weather conditions. However, higher ventilation rates were more effective for reducing potential pathogen dispersal. Published by Elsevier Ltd on behalf of IAgrE.