Integration of a mathematical model approach with hazard and operability (HAZOP) analysis is presented in this contribution. The presented analysis is based on the mathematical modelling of a process unit, where both the steady-state analysis (including continuation and bifurcation analyses), and the dynamic simulation are used. The main benefit of this integration is the ability to perform a detail safety analysis for a relatively complicated process. Such an approach may dramatically decrease the possibility that several sources of hazard will be overlooked. Of course, the presented methodology may also seriously reduce the time necessary for the hazard identification process. In this paper, a methyl tertiary-butyl ether (MTBE) production unit was chosen to identify potential hazard and operational problems of a real process. This simplified case-study unit consists of two investigated types of equipment: a tubular fixed bed reactor and a reactive distillation column. (c) 2007 Elsevier Ltd. All rights reserved.