Windows have a considerable influence on the thermal balance of buildings. The aim of the present work is to evaluate the performance of a photochromic window (PCW) in terms of building's energy demands and natural lighting. In these windows, a fundamental role is played by the solar transmission coefficient, which can change depending on the incident solar radiation. A comparison is made with the case of using clear double glazing and low emissivity (Low-E) windows. The analysis is performed using EnergyPlus, where a laboratory of DIMEG, University of Calabria (Rende, Italy) is modelled. The model is calibrated to be representative of reality and can be used to compare different types of windows under the same external conditions. Results are obtained for a south-facing window, varying its size. The results show, for this location in southern Italy, that the PCW allows a reduction in annual energy consumption compared to the clear window (up to 9.3%) and compared to the Low-E window (up to 4.1%). The daylight provided by the PCW is greater than the other two solutions and, in some cases, also reduces the risk of glare.