The study investigates a critical application in the field of energy demand for air-conditioning: the health care facilities. These buildings are quite energy-intensive, because of necessity of high microclimatic control, need of numerous air changes and, contemporarily, strict set points required for temperature and relative humidity. The achievable energy savings by improving the thermal-physical characteristics of the building envelope are examined, with reference to a medium-size hospital, located in Mediterranean climate. The indoor comfort conditions have been analyzed as well as the reduction of energy demands, depending on the HVAC system. Indeed, the active plants are characterized by quite different energy demands, due to different achievable quality of microclimatic control and indoor air. The refurbishment of the building envelope, as demonstrated, is always convenient, by considering all possible point of views, and thus energy savings, better indoor microclimate, reduction of polluting emissions, technical and economical feasibility. Finally, even if ventilation loads induce the highest heating and cooling demands, however the envelope refurbishment is an effective retrofit action. (C) 2013 Elsevier B.V. All rights reserved.