The present paper deals with the establishment of a new methodology in order to evaluate the inherently safer characteristics of a continuous intensified reactor in the case of an exothermic reaction. The transposition of the propionic anhydride esterification by 2-butanol into a new prototype of "heat-exchanger/reactor", called open plate reactor (OPR), designed by Alfa Laval Vicarb has been chosen as a case study. Previous studies have shown that this exothermic reaction is relatively simple to carry out in a homogeneous liquid phase, and a kinetic model is available. A dedicated software model is then used not only to assess the feasibility of the reaction in the "heat-exchanger/reactor" but also to estimate the temperature and concentration profiles during synthesis and to determine optimal operating conditions for safe control. Afterwards the reaction was performed in the reactor. Good agreement between experimental results and the simulation validates the model to describe the behavior of the process during standard runs. A hazard and operability study (HAZOP) was then applied to the intensified process in order to identify the potential hazards and to provide a number of runaway scenarios. Three of them are highlighted as the most dangerous: no utility flow, no reactant flows, both stop at the same time. The behavior of the process is simulated following the stoppage of both the process and utility fluid. The consequence on the evolution of temperature profiles is then estimated for a different hypothesis taking into account the thermal inertia of the OPR. This approach reveals an intrinsically safer behavior of the OPR. (C) 2008 Elsevier Ltd. All rights reserved.