We report here an accurate surface organometallic chemistry (SOMC) approach to propane oxidative dehydrogenation (ODH) using a μ2-oxo-bridged, bimetallic [V2O4(acac)2] (1) (acac = acetylacetonate anion) complex as a precursor. The identity and the nuclearity of the product of grafting and of the subsequent oxidative treatment have been systematically studied by means of FT-IR, Raman, solid-state (SS) NMR, UV-vis DRS, EPR and EXAFS spectroscopies. We show that the grafting of 1 on the silica surface under a rigorous SOMC protocol and the subsequent oxidative thermal treatment lead exclusively to well-defined and isolated monovanadate species. The resulting material has been tested for the oxidative dehydrogenation of propane in a moderate temperature range (400-525 °C) and compared with that of silica-supported vanadium catalysts prepared by the standard impregnation technique. The experimental results show that the catalytic activity in propane ODH is strongly upgraded by the degree of isolation of the VOx species that can be achieved by employing the SOMC protocol. © 2016 American Chemical Society.