This chapter focuses on Villa Medici La Petraia (UNESCO World Heritage), built in the XV century in Florence, Italy. The relevance of this study case is due to a specific intervention that, during the XIX century, heavily influenced indoor microclimate: the addition of a glass and cast iron cover on the central courtyard. The change of status of this space, from outdoor to indoor, had an important effect on the whole microclimate of the Villa, as well as several other interventions including the addition of stoves and other systems of central heating. Finally, in the XX century, the Villa become a museum and no HVAC system has been added since then. On this specific case was carried on an extensive and complete analysis, including: archival research for historic documents; survey of the building and of the HVAC systems; monitoring of indoor microclimate in three different spaces, including the covered courtyard; software modeling and calibration of the model; construction past configurations, with and without covering in the courtyard, and analysis of the associated microclimate; up to the suggestion of management solutions for microclimatic issues. Where the study case of the Malatestiana Library, presented in Chapter 8, has been the beginning of the research on HIM, the case of Villa La Petraia represents a fully developed analysis of indoor microclimate, giving some sort of standard on how to perform these kind of studies and increasing the knowledge on HIM in general and on simulations and the prediction of future microclimatic conditions in particular.