The HVAC systems for operating rooms are energy-intensive and sophisticated in that they operate 24 hours per day year-round and use large amount of fresh air to deal with infectious problems and to dilute microorganisms. However, little quantitative information has been investigated about trade-off between energy-efficient HVAC system and indoor environment quality especially when the operating room is not occupied. The objective of this study is to present the field measurement approach on performance evaluation of the HVAC system for an unoccupied operating room. Variable air volume terminal boxes were conducted to verify the compromise of energy-saving potential and indoor environment parameters including particle counts, microbial counts, pressurization, temperature and humidity. Field measurements of a full-scale operating room have been carried out at a district hospital in Taiwan. Numerical simulation has been applied to evaluate the air flow distribution and concentration contours while conducting the velocity reduction approach in the unoccupied operating room. The results reveal that it is feasible to achieve satisfactory indoor environment by reducing the supply air volume (or velocity) in the unoccupied operating room. Optimal face velocity of HEPA filter and percentage of damper opening for the variable air volume terminal boxes could be obtained through compromising of indoor environment quality control and energy consumption as well. It will stimulate a more robust investigation of infection-controlled, energyefficient and environment-comfortable HVAC system specific for unoccupied operating rooms.