Nowadays, energy saving is considered a key issue worldwide, as it brings a variety of benefits: reducing greenhouse gas emissions, reducing demand for energy imports, and lowering costs on a household and economy-wide level. Researchers and building designers are looking to optimize building efficiency by means of new energy technologies. Changes in existing buildings can also be made to reduce energy consumption and costs. These may include the usage of new heat transfer fluids based on nanofluids. In this work, an extended experimental campaign (from February 2020 to March 2021) has been carried out on an educational building in the Campus of University of Salento, Lecce – Italy, in order to evaluate the increase in performance of the HVAC system, due to the usage of a nanofluid. The results show that, under optimal operating conditions, plant performance improves more than 10%, with average daily peaks of about 15%.