For the processing industries, it is critically to have an economically optimum and inherently safer design and operation. The basic concept is to achieve the best design based on technical and business performance criteria while performing within acceptable safety levels. Commonly, safety is examined and incorporated typically as an after-thought to design. Therefore, systematic and structured procedure for integrating safety into process design and optimization that is compatible with currently available optimization and safety analysis methodology must be available. The objective of this paper is to develop a systematic procedure for the incorporation of safety into the conceptual design and optimization stage. We propose the inclusion of the Dow fire and explosion index (F&EI) as the safety metric in the design and optimization framework by incorporating F&EI within the design and optimization framework. We first develop the F&EI computer program to calculate the F&EI value and to generate the mathematical expression of F&EI as a function of material inventory and operating pressure. The proposed procedure is applied to a case study involving reaction and separation. Then, the design and optimization of the system are compared for the cases with and without safety as the optimization constraint. The final result is the optimum economic and inherently safer design for the reactor and distillation column system. (C) 2006 Published by Elsevier Ltd.