Vanadium-magnesium oxide (VMgO) catalysts have been prepared, characterized and tested in the ODH of n-butane. The catalysts were prepared by two variations of the wet-impregnation method using aqueous ammonium metavanadate or organically-based methanolic vanadyl acetylacetonate solutions. The catalyst surface area depends on the vanadium content and the preparation method. Catalyst characterization (i.e. XRD, V-51 NMR, FTIR, LRS) results indicate the presence of poor crystalline Mg-orthovanadate (Mg3V2O8), while the presence of other Mg-vanadates is not clear. Oxygen isotopic-exchange experiments on VMgO catalysts indicate an R-2 process : [O-18(2)+2(16)O((s))(2-)-->((OOOO)-O-18-O-18-O-16-O-16)((s))(4-)-->2(18)O((s))(2-)+O-16(2(g))] at temperatures higher than 1023 K, while an R-0-type [O-18(2(g))+O-16(2(g))-->2(16)O(18)O((g))] is observed at 823 K, as a consequence of a small activity for homophase isotopic. Both the catalytic activity and the selectivity to oxydehydrogenation products depend on the vanadium content but is independent on the catalyst preparation method. This behavior is observed in the ODH of n-butane with both O-2 and N2O. However, while conversion of n-butane was higher when using O-2 as oxidant, the selectivity to C-4-olefins was higher with N2O as oxidant. Pulse experiments show that prereduced surfaces are not effective in producing olefins while selective catalysts are achieved with preoxidized surface. A mechanism for the oxidative dehydrogenation of n-butane is proposed.