An approach to reduce the probability of producing a domino effect in process industry is developed in this work. It is assumed that optimal layouts should include appropriate analysis to reduce risk during the process design stage. The model developed for this approach combines the estimation of probability of damage due to overpressure, proposed by Mingguang and Juncheng (2008), and escalation threshold values defined by Cozzani, Gubinelli, and Salzano (2006). These equations are combined with other typical layout constraints as well as bounding the probability constraint, which has resulted in a highly non-linear MINLP problem. Solving a case study used by other authors provides evidence for reliability of the developed approach. In this way, layouts are designed to reduce the escalation probability yielding safe distributions. (C) 2012 Elsevier Ltd. All rights reserved.