In this study, a simulation-aided effective design of a catalytic reactor for ethane oxidative dehydrogenation is presented. The reactor model was based on a previously developed mechanistic model describing the kinetics of the reaction over the Ni0.85Nb0.15Ox catalyst. The main objective of the work was to define the optimum operating conditions, i.e. temperature range, pressure, C2H6/O-2 ratio, reactant mixture density and oxygen admission mode, in order to maximize the ethylene yield of the process. Based on this parametric study, it was found that maximum ethylene yield can be achieved at atmospheric pressure and at temperatures in the range of 300-350 degrees C, using as feed a mixture of 10% C2H6-5% O-2 (C2H6/O-2 ratio equal to 2) when air is used as oxidation medium. Staged oxygen admission in the reactor was extensively studied and the simulation data demonstrated the possibility of achieving high selectivity at high ethane conversion. The introduction of oxygen in a stepwise manner via 15 injection points throughout the catalytic bed led to an increase in ethylene selectivity by 8% compared to the conventional co-feed mode. Moreover, simulation of a staged oxygen admission with 4 injection points, a more realistic configuration for industrial application, showed that the use of a multi-compartment reactor with intermediate oxygen addition reduces the cooling demands by about 17%. (C) 2017 Elsevier B.V. All rights reserved.