The partial oxidation of n-butane to maleic anhydride over a vanadium-phosphorus oxide (VPO) catalyst has been studied in reactors with separation of the oxidizing and reducing zones. In the two-zone fluidized bed reactor (TZFBR) and in the internal circulating fluidized bed reactor (ICFBR), oxygen and n-butane are fed at different points of a single vessel, obtaining separated zones for catalyst oxidation and n-butane reaction. These configurations allow working at relatively high n-butane concentrations without being within the flammability range and permitting strict control of the catalyst performance, which will result in improvements in selectivity to the desired product. In this work, a detailed study of the main operating variables is presented, as well as an upscaling from laboratory to bench scale.