Heating, Ventilation and Air Conditioning (HVAC) systems consist one of the main elements that have a significant impact to both occupants' comfort and energy consumption in tertiary buildings, affecting therefore productivity and operational cost respectively. Energy consumption depends on occupant comfort through the calculation of the thermal comfort function, a function which derives from an extended analysis that takes into account various parameters such as temperature, humidity, air velocity, activity and clothing. This paper examines the implementation of a multi-criteria algorithm for optimizing operational control of HVAC systems, by integrating multiple real-time condition variables as input and targeting maximization of occupants' comfort satisfaction and minimization of energy consumption as output. As added value, the proposed framework allows its users to configure themselves the balance between comfort and consumption by adjusting specific thresholds. The effectiveness of the optimization algorithm is presented through the real-time operation of an HVAC system in an office building. Experimental results are presented and conclusions regarding the value of the HVAC optimal operational control are derived.