The syntheses, solid state, spectroscopic and potentiometric solution characterizations of VO(acac-NH₂)₂ (acac-NH₂ = acetylacetamido) and VO(acac-NMe₂)₂ (acac-NMe₂ = N,N-dimethylacetylacetamido) have been investigated. In VO(acac-NMe₂)₂ the vanadium ion exhibits a distorted square pyramidal coordination environment. Crystals of VO(acac-NMe₂)₂ are monoclinic and structural studies were carried out. EPR and UV-visible spectroscopic and potentiometric methods were used to characterize the speciation, complex stability and structures in both aqueous and organic solutions. VO(acac-NH₂)₂ and VO(acac-NMe₂)₂ each form two species in solution: a 1 ∶ 2 and a 1 ∶ 1 metal ∶ ligand complex. The complexes formed from VO(acac-NH₂)₂ are slightly more stable than those of VO(acac-NMe₂)₂; however, VO(acac)₂ forms more stable complexes. In non-coordinating solvents the 1 ∶ 2 complexes maintain a five-coordinate vanadium atom, whereas in coordinating solvents such as water and pyridine the complexes become six-coordinate. Based on the similarity of the EPR parameters of VO(acac-NH₂)₂ with those of the VO(acac)₂ complex, it is likely these species contain the coordinating solvent added trans to the VO bond. These new VO(acac)₂ derivatives are improved with respect to water solubility. Although the solution stability is not as good as that of VO(acac)₂, it is higher than that of VO(acac-R)₂ (R = CH₃ or C₂H₅). Thus, should the stability of the 1 ∶ 1 complex be important for the compound’s efficacy, both of these new complexes would be predicted to be less effective than VO(acac)₂ but more effective than VO(acac-Et)₂ (acac-Et = 3-ethylacetylacetonate) in lowering glucose levels in streptozotocin-induced diabetic rats.