Reactions comprised of oxygen transfer in conjunction with the abstraction of two fluorine atoms from difluoromethane are observed in the gas-phase chemistry of various selected vanadium oxide cluster ions. These studies were performed on a triple quadrupole mass spectrometer coupled with a laser vaporization source. Aside from the oxygen transfer reactions, channels for the loss of molecular oxygen and the association of CH2F2 to the clusters were also observed. For example, the cluster V3O7+ reacted with CH2F2 to produce V3O6F2+ in addition to the association product V3O7. CH2F2+ with both channels occurring under single collision conditions and near thermal energies at ambient temperature. The vanadium oxide species V2O4-6+, V3O6-8+, V4O8-11+, V5O11-13+, V6O13-15+, and V7O16-18+ were individually selected and their reactivities compared by examining the relative product branching ratios. The reactivity of the VxOy+ species with difluoromethane displayed a distinct dependence on the size of the clusters. The smaller clusters were most reactive while the larger clusters were observed to be inert toward reaction with difluoromethane with the exception of the oxygen-rich clusters, which simply lost molecular oxygen upon collision with the reactant gas.