A methodology based on key performance indicators was developed and applied to the design of sustainable industrial processes. The methodology provides a procedure for the definition of a dynamic set of quantitative key performance indicators suitable to capture the environmental, economic and societal impacts of process options, thus, tracing the sustainability footprint of alternatives. The preliminary design of a production plant for cyclohexanone is presented as the leading case in the discussion. The influence of design choices on environmental impact profiles, economic efficiency and inherent safety performance was pointed out. The application evidenced that the definition of appropriate indicators may have an important added value in supporting design activities, both for the correct assessment of alternative options and for the proactive identification of design improvements. (C) 2011 American Institute of Chemical Engineers AIChE J, 57: 3063-3084, 2011