The performance of a ventilation system affects air quality, thermal comfort, and energy consumption in indoor environments. To evaluate the performance of displacement ventilation under various room configurations, steady Reynolds Averaged Navier–Stokes (RANS) Computational Fluid Dynamics (CFD) simulations were used. The CFD model was validated using measurements of a full-scale test room. The age of air concept was used to evaluate the ventilation performance regarding indoor air quality. The PD index was used to control the case studies for draft risk. Twelve cases with different configurations were systematically studied and compared with the reference case. The configurations included plan aspect ratio, exhaust opening position, inlet position and geometry, and internal heat gains. The results showed that the overall ventilation performance of a room is less sensitive to room configurations compared with local ventilation performance around the occupants. However, almost in all cases, the occupants were exposed to better-than-average air quality in most cases. The results also indicated that when internal heat gains are small, displacement ventilation should be used with caution. Practical application Any HVAC system design is based on assumptions made for ventilation performance. Comprehensive knowledge of the influential factors is critical for an efficient design. Regarding the architecture and interior design, the architects are also involved in the ventilation systems since they have an axial role in decision making for room configuration, including but not limited to room geometry, the position of inlet and outlet air terminals, and heat/pollutant sources. Consequently, the impact of room configuration on ventilation performance is of practical importance in the architecture, engineering, and construction industry.