The Schiff base N,N′‐ethylenebis(pyridoxylideneiminato) (H2pyr2en, 1) was synthesized by reaction of pyridoxal with ethylenediamine; reduction of H2pyr2en with NaBH4 yielded the reduced Schiff base N,N′‐ethylenebis(pyridoxylaminato) (H2Rpyr2en, 2); their crystal structures were determined by X‐ray diffraction. The totally protonated forms of 1 and 2 correspond to H6L4+, and all protonation constants were determined by pH‐potentiometric and 1H NMR titrations. Several vanadium(IV) and vanadium(V) complexes of these and other related ligands were prepared and characterized in solution and in the solid state. The X‐ray crystal structure of VVO2(HRpyr2en) shows the metal in a distorted octahedral geometry, with the ligand coordinated through the N‐amine and O‐phenolato moieties, with one of the pyridine‐N atoms protonated. Crystals of (VVO2)2(pyren)2⋅2 H2O were obtained from solutions containing H2pyr2en and oxovanadium(IV), where Hpyren is the “half” Schiff base of pyridoxal and ethylenediamine. The complexation of VIVO2+ and VVO2+ with H2pyr2en, H2Rpyr2en and pyridoxamine in aqueous solution were studied by pH‐potentiometry, UV/Vis absorption spectrophotometry, as well as by EPR spectroscopy for the VIVO systems and 1H and 51V NMR spectroscopy for the VVO2 systems. Very significant differences in the metal‐binding abilities of the ligands were found. Both 1 and 2 act as tetradentate ligands. H2Rpyr2en is stable to hydrolysis and several isomers form in solution, namely cis–trans type complexes with VIVO, and α‐cis‐ and β‐cis‐type complexes with VVO2. The pyridinium‐N atoms of the pyridoxal rings do not take part in the coordination but are involved in acid–base reactions that affect the number, type, and relative amount of the isomers of the VIVO–H2Rpyr2en and VVO2–H2Rpyr2en complexes present in solution. DFT calculations were carried out and support the formation and identification of the isomers detected by EPR or NMR spectroscopy, and the strong equatorial and axial binding of the O‐phenolato in VIVO and VVO2 complexes. Moreover, the DFT calculations done for the VIVO(H2Rpyr2en) system indicate that for almost all complexes the presence of a sixth equatorial or axial H2O ligand leads to much more stable compounds. Vanadium complexes of Schiff‐base and reduced‐Schiff‐base ligands derived from the reaction of pyridoxal and ethylenediamine are remarkable examples of the complexity of the types of isomers that may form in solutions containing VIVO and VVO2 complexes (see picture for the NMR spectra).