The practice of inherent safety in process development and design asks for reliable and systematic assessment tools. In the present study, a novel quantitative approach developed fir the inherent safety assessment of process flow diagrams in early design stages is presented. The output of the approach is a metric that quantifies the inherent safety fingerprint of the process scheme by a set of key performance indicator. Physical parameters are used for The quantification of the hazard deriving from materials, process conditions and equipment characteristics. The assessment resorts to the identification and modeling of credible accident consequences on humans and equipment. The adoption of tangible parameters based on consequence modeling yields a clear and sound picture of the inherent safety performance of a design option. An example of application focused on some envisaged options of the hydrogen supply chain (production, distribution, and utilization) is presented. (C) 2009 American Institute of Chemical Engineers Process Saf Prog 28: 156-170, 2009