The energy optimization method of HVAC system from a holistic perspective for the energy optimal selection of the HVAC system for an operating theater is presented in the article. All subsystems and the HVAC system as a whole are described in the vector form, whereas the sets of all the possible subsystems and systems variants as a whole are described in the matrix form as a constant parameters function and decision variables function. The system analysis and matrix calculus are applied in order to determine the sets of acceptable subsystems and systems variants. The total review of acceptable solutions methods with the use of the objective function is applied as the method for the optimal variant determination. The objective function is the annual primal energy demand for each acceptable system based on the simulation models. It has been shown that as a result of the HVAC system structure optimization, savings in the annual primary energy demand can be achieved of 4.4-6.5% - for thermodynamic processing and of 2.5-4.3%- in total for transfer and thermodynamic processing of air. It has also been shown that for an optimal structure of the HVAC system, the extension of the admissible tolerance range of relative humidity in the operating room from 50% ("on point") to 40-60%, allows to achieve primary energy savings of 34.9% - for thermodynamic processing and of 22.8% - in total for transfer and thermodynamic processing of air.