Italian cities are mainly constituted by buildings constructed until the mid-20th century by pre-industrial construction techniques. A HVAC system for the energy retrofit of historical buildings is evaluated when applied in the case study of Sant’Apollinare. It consists of a ground source heat pump a water tank for thermal energy storage connected to a low-temperature radiant system and air handling unit. The building thermal-energy behavior, typically influenced by thermal inertia in historical buildings, and the novel HVAC system performance interactions are comparatively assessed together with more traditional scenarios. Energy demand decreases by about one third compared to the pre-retrofit situation.