Electrospray ionization (ESI), tandem-mass spectrometry, and collision-induced dissociation (CID) were used in this study to generate and investigate vanadyl [VO²⁺] complexes containing various alkoxide and nitrile ligands. The precursor ions explored were of the general formula [VO(RO)(L)₂]⁺, where RO represents an alkoxide generated from its respective alcohol (methoxide, ethoxide, 1-propoxide, or 1-butoxide) and L represents one of the following nitrile ligands: acetonitrile, propionitrile, butyronitrile, or benzonitrile. These precursor ions were isolated and subjected to CID, which produced various fragmentation pathways, respective to the coordinated alkoxide. When dissociated, all precursor ions exhibited the elimination of a single nitrile ligand, followed by the addition of H₂O or O₂, such that the general formulae of the fragment ions at the MS² stage were [VO(RO)(L)]⁺, [VO(RO)(L)(H₂O)]⁺, and [VO(RO)(L)(O₂)]⁺. CID of [VO(RO)(L)]⁺ resulted in fragmentation pathways exclusive to the alkoxide present in the molecule, though similarities exist among complexes containing ethoxide, 1-propoxide, and 1-butoxide; such as a loss of H₂ and the subsequent formation of an enolate ligand from the alkoxide. Complexes containing 1-butoxide exhibited exclusive CID pathways involving the production of methoxide-containing complexes as well as complexes containing ethynoxide.