The choice of chemical process routes is one of the key decisions in the early design stages. An "inherently safer" route will help eliminate many hazards as well as obviate many risk control devices. Many inherent safety indices have been proposed to quantify hazards, health and environmental impact of a chemical process route. These indices measure a route's inherent benign-ness based on various process route descriptors such as temperature, pressure, yield, as well as the properties of the chemicals involved. Usually routes involving more reactive, toxic chemicals and hazardous reactions are considered less safe by these indices. Inherent safety indices typically suffer from several shortcomings including subjective scaling and weighting of factors, and consideration of limited set of aspects. In this paper, we propose the Inherent Benign-ness Indicator (IBI), a statistical analysis-based methodology for comparing process routes. A systematic way to scale disparate factors is also proposed. The IBI can be used to rank the routes; additionally it can determine the broad similarities and differences in the safety, health, and environmental footprints of the routes. Thus, it can assist the process designer determine modifications needed to improve a route's benign-ness. This easy-to-use, extendable, theoretically sound approach to compare competing routes is illustrated using two case studies involving acetic acid and methyl methacrylate manufacture. (c) 2007 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.