Significant attention is currently being paid to reducing building energy demand and improving indoor thermal conditions, as required by European directives. In school buildings, a significant part of the winter energy demand is related to high airflow rates required for ventilating classrooms. Moreover, the correlation between comfortable indoor thermal-hygrometric conditions, healthy indoor air quality and satisfying student performance is well known. Few research works have investigated different types of air conditioning systems for typical school buildings, from the point of view of both energy and thermal-hygrometric performances. This kind of analysis is carried out in this paper. A typical school building located in southern Italy is analysed by using dynamic building energy simulation software. Different types of heating, ventilation and air conditioning (HVAC) systems are simulated for both winter and summer conditions. Indoor air temperature, relative humidity and predicted mean vote values are evaluated. The annual energy requirements, energy costs and related emissions are calculated. Finally, a multi-criteria analysis for the examined HVAC systems is proposed, considering different weighting for the main performance criteria (winter thermal comfort, plant costs, energy costs and emissions), in order to support decision making.