Sustainability is becoming more important in numerous industries, including healthcare. Action to achieve sustainability is undertaken by various means, such as the Green Deal Healthcare. Several tools exist that can assess the environmental impact of a certain industry or company, but no tools exist that aid in actively lowering this environmental impact. Therefore, the HSMEA (Healthcare Sustainability Mode and Effect Analysis) tool was developed. This method is based on the Lean philosophy and HFMEA (Healthcare Failure Mode and Effect Analysis) tool and consists of six steps that aid in making a healthcare process more sustainable, in terms of waste production, energy use, or water use. With this tool, processes that contribute to these factors are identified in a highly structured and systematic way, and practical solutions are created and executed for these situations by a multidisciplinary team. This tool was validated in the academic hospital in Leiden, the Netherlands (Leids Universitair Medisch Centrum). Next, it was applied to two clinical case studies, assessing two processes that are currently present in the operating rooms of the LUMC. The HSMEA tool showed that with the implementation of four solutions, great improvements can be achieved in terms of waste and CO2-equivalents production and recycling rate. These four interventions are currently being implemented in the LUMC. This novel sustainability tool has therefore proved its usefulness and clinical applicability in a healthcare setting. By implementing this tool throughout the hospital, it will support the hospital reaching its sustainability goals.