A new preparative route for vanadium phosphate catalysts is described using supercritical CO2 as an antisolvent. The amorphous microspheroidal VPO produced is shown to be more active than comparable crystalline VPO catalysts for the selective oxidation of n-butane to maleic anhydride and, furthermore, does not require an extensive pretreatment or activation period to establish full catalytic activity. VPO catalysts prepared using supercritical CO2 as an antisolvent maintain their amorphous nature throughout the catalyst test period. In contrast, amorphous VPO catalysts can also be prepared by using liquid CO2 as antisolvent or by solvent evaporation in vacuo; however, these materials are found to partially crystallise during the oxidation of n-butane. The wholly amorphous catalysts are characterised using transmission electron microscopy, X-ray absorption spectroscopy, P-31 spin-echo mapping, NMR spectroscopy, and X-ray photoelectron spectroscopy. The role of amorphous material in vanadium phosphate catalysis is discussed in detail.