The article presents the status quo regarding the requirements and structures of HVAC (Heating, Ventilation, Air Conditioning) systems in highly aseptic operating rooms, as well as the energy costs associated with operating these systems for alternative air supply solutions. In this regard, it specifically addresses the discussion on selecting the optimal air supply system from a hygienic and energy perspective. The results of simulation calculations of the annual usable, final, and primary energy requirements, as well as the energy costs for the HVAC system in a typical highly aseptic operating room, are presented, along with two alternative air supply system variants: Variant I, with a laminar air flow ceiling (LAV), and Variant II, with a perimeter diffuser. It was shown, among other things, that the annual demand for primary energy and the energy costs of thermodynamic treatment and air circulation for the HVAC system of the operating room for variant II – with a perimeter diffuser, are 9% lower compared to variant I – with a laminar ceiling, with the same technological and hygienic requirements.