Cool materials are a well established solution to mitigate urban overheating. Notwithstanding, their net energy and cost impact might turn negative in year-round assessments, owing to space heating penalties. Thermochromic materials, that are able to switch from a prevalent absorbing to a prevalent reflective behaviour, may overcome this problem. Several studies at the material level show advantages and limits of the technology, however no marketable solution exists yet. This study aims at quantifying the energy saving potential of switching cool roofs to optimize the thermal response of residential buildings in the Mediterranean Basin. The task is performed by simulation in transient regime, drawing on different material modelling approaches. The analysis is carried out in three cities: Barcelona, Palermo and Cairo, representative of different areas of the Basin. Several scenarios are considered, different in terms of building insulation, transition temperature and switching magnitude. Thermochromic materials exhibit potential annual energy savings up to 8.5% and 19% with respect to cool and conventional roofs, respectively, when the solar reflectance switches from 0.15 to 0.75. Smaller annual energy savings are achieved as the switching magnitude is decreased. Due to several factors, thermochromic cool roof can also lead to annual energy penalties compared to static roofs. Further modelling and experimental efforts are needed to better predict the response of the material during the transition phase and refine the optimization process.