Safety and performance are important factors in the design and operation of chemical plants. This paper describes the formulation of a mixed integer nonlinear programming model for the optimization of plant layout with safety considerations. The model considers a quantitative risk analysis to take safety into account, and a bowtie analysis is used to identify possible catastrophic outcomes. These effects are quantified through consequence analyses and probit models. The model allows the location of facilities at any available point, an advantage over grid-based models. Two case studies are solved to show the applicability of the proposed approach. (C) 2014 Elsevier Ltd. All rights reserved.