The effect of catalyst pore structure on n-butane oxidation to maleic anhydride in a fixed-bed reactor was investigated by numerical simulations. The micro- and macro- pore model of Wakao and Smith was applied to model the diffusion–reaction inside the catalyst pellet. The studied pore structure parameters were macro-pore porosity, mean macro-pore diameter and mean micro- pore diameter. A fixed-bed reactor was simulated with a detailed two-dimensional heterogeneous model under typical industrial conditions. Simulation results have demonstrated that the reactor performance is sensitive to the chosen pore structure parameters especially macro-pore porosity and mean micro-pore diameter. A bi-modal catalyst pellet with bigger macro-pores and smaller micro-pores is favored to achieve higher yields of maleic anhydride. This work highlights the potential of improving this process by pore structure optimization.