This paper presents a mixed integer nonlinear programming (MINLP) model to improve the computational use of the layer of protection analysis (LOPA). For a given set of independent protection layers to be implemented in a process, the proposed optimization model is solved to: a) Include costs associated with the different prevention, protection and mitigation devices, and b) Satisfy the risk level typically specified in the LOPA analysis through the occurrence probability. The underline purpose focuses on improving the analysis process and decision making to obtain the optimal solution in the safeguards selection that satisfies the requirements to be considered as IPL's. The optimization is based on economic and risk tolerance criteria. As a first stage of this proposal, the safety instrumented system (SIS) design is optimized so that the selection of SIS components minimizes the risk and satisfies the safety integrity level (SIL) requirements. A case study is presented to validate the whole proposed approach. (C) 2012 Elsevier Ltd. All rights reserved.