Topic of the study is the investigation of potentialities of energy simulation for optimizing the building refurbishment, by taking into account impacts of both envelope renovation and HVAC system selection. Energy audit and refurbishment of the Day-Hospital building of a great Italian health care facility are proposed. A meticulous energy diagnosis of the base case building and design of a complete renovation-by improving both building envelope and HVAC systems-are presented. All data and boundary conditions for dynamic energy investigations have been carefully selected, also by means of in-situ studies, in order to provide a reliable model. In particular, several energy efficiency measures, with reference to building envelope and HVAC systems, are analyzed and it will be evidenced that, step-by-step, a proper design, supported by the adoption of numerical studies, may optimize the energy performances of the building, as well as the indoor microclimatic control.