The reactions between o-vanillin and three isomeric aminopyridines lead to imines of diverse spatial conformation and reactivity. The direct products of these simple reactions carried out in methanol are either imine compounds formed in the reactions of 2-amino-and 3-aminopyridine with o-vanillin or the α-aminoether formed in the reaction of o-vanillin with 4-aminopyridine. The Schiff-type derivative of 4-aminopyridine and o-vanillin, which is described in this paper for the first time, is very reactive and can only be obtained indirectly from the α-aminoether in anhydrous conditions. All compounds are characterized by X-ray diffraction and FT-IR and NMR spectroscopies. The DFT calculations at all-electron BLYP/Q4ZP level of theory are utilized to explain the differences between the reactivity of isomeric aminopyridines and their imine derivatives.