The oxidation of n-butane to maleic anhydride was investigated over a series of model-supported vanadia catalysts where the vanadia phase was present as a two-dimensional metal oxide overlayer on the different oxide supports (TiO2, ZrO2, CeO2, Nb2O5, Al2O3, and SiO2), No correlation was found between the properties of the terminal V=O bond and the butane oxidation turnover frequency (TOF) during in situ Raman spectroscopy study, Furthermore, neither the n-butane oxidation TOF nor maleic anhydride selectivity was related to the extent of reduction of the surface vanadia species, The n-butane oxidation TOF was essentially independent of the surface vanadia coverage, suggesting that the n-butane activation requires only one surface vanadia site. The maleic anhydride TOF, however, increased by a factor of 2-3 as the surface vanadia coverage was increased to monolayer coverage, The higher maleic anhydride TOF at near monolayer coverages suggests that a pair of adjacent vanadia sites may efficiently oxidize n-butane to maleic anhydride, but other factors may also play a contributing role (increase in surface Bronsted acidity and decrease in the number of exposed support cation sites). Varying the specific oxide support changed the n-butane oxidation TOF by ca, 50 (Ti > Ce > Zr similar to Nb > Al > Si) as well as the maleic anhydride selectivity, The maleic anhydride selectivity closely followed the Lewis acid strength of the oxide support cations, Al > Nb > Ti > Si > Zr > Ce. Tile addition of acidic surface metal oxides (W, Nb, and P) to the surface vanadia layer was found to have a beneficial effect on the n-butane oxidation TOF and the maleic anhydride selectivity, The creation of bridging V-O-P bonds had an especially positive effect on the maleic anhydride selectivity.