This paper analyzes the impact of a change in the thermal insulating material on both the energy and environmental performance of a building, evaluated through two different green building assessment methods: Leadership in Energy and Environmental Design (LEED) and Istituto per l’innovazione e Trasparenza degli Appalti e la Compatibilità Ambientale (ITACA). LEED is one of the most qualified rating systems at an international level; it assesses building sustainability thanks to a point-based system where credits are divided into six different categories. One of these is fully related to building materials. The ITACA procedure derives from the international evaluation system Sustainable Building Tool (SBTool), modified according to the Italian context. In the region of Umbria, ITACA certification is composed of 20 technical sheets, which are classified into five macro-areas. The analysis was developed on a residential building located in the central Italy. It was built taking into account the principles of sustainability as far as both structural and technical solutions are concerned. In order to evaluate the influence of thermal insulating material, different configurations of the envelope were considered, replacing the original material (glass wool) with a synthetic one (expanded polystyrene, EPS) and two natural materials (wood fiber and kenaf). The study aims to highlight how the materials characteristics can affect building energy and environmental performance and to point out the different approaches of the analyzed protocols.