The oxidation of n-butane to maleic anhydride was investigated over model Nb-, Si-, Ti-, V-, and Zr-promoted bulk VPO and supported vanadia catalysts. The promoters were concentrated in the surface region of the bulk VPO catalysts. For the supported vanadia catalysts, the vanadia phase was present as a two-dimensional metal oxide overlayer on the different oxide supports (TiO2, ZrO2, Nb2O5, Al2O3, and SiO2). No correlation was found between the electronegativity of the promoter or oxide support cation and the catalytic properties of these two catalytic systems. The maleic anhydride selectivity correlated with the Lewis acidity of the promoter cations and oxide supports. Both promoted bulk VPO and supported vanadia catalysts containing surface niobia species were the most active and selective to maleic anhydride. These findings suggest that the activation of n-butane on both the bulk and supported vanadia catalysts probably requires both surface redox and acid sites, and that the acidity also plays an important role in controlling further kinetic steps of n-butane oxidation.