Vanadium aluminophosphates with AFI structure (VAPO-5) have been prepared by hydrothermal synthesis, characterized by several physicochemical techniques (i.e., thermogravimetric analysis, XRD, Solid state MAS NMR, UV-Vis, EPR, TPR), and tested for the oxidative dehydrogenation of propane. The influence of the different synthesis parameters, particularly the content and oxidation state of vanadium, the pH of the gel, and the presence of complexing agents, has been studied. The vanadium atom are incorporated as isolated vanadyl VO2+ ions in square pyramidal or distorted octahedral environments. After calcination in air, most of the V4+ ions are oxidized to V5+ in square pyramidal or octahedral symmetry, which evolve toward tetrahedral coordination upon dehydration. The VAPO-5 samples are active and selective for the oxidative dehydrogenation of propane. Their catalytic properties are better than the corresponding ALPO(4)-5 supported vanadium catalysts. Isolated tetrahedral V5+ species in the framework of AFI structure are proposed to be the active and selective sites for the oxydehydrogenation of propane.