Vapor-phase aldol condensation of methyl acetate with formaldehyde over vanadium phosphorus oxide (VPO) deposited on SiO 2 , TiO 2 , ZrO 2 , Nb 2 O 5 , Sb 2 O 3 , γ-Al 2 O 3 , and n-γ-Al 2 O 3 (γ-Al 2 O 3 treated with H 3 PO 4 ) for methyl acrylate production was developed. The VPO/n-γ-Al 2 O 3 was found to have the best performance based on the evaluated experiments in a fixed-bed reactor. The physicochemical properties of the catalysts were investigated by different characterization methods such as the Brunauer−Emmett−Teller method, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, H 2 temperature programmed reduction, Fourier transfrom infrared spectroscopy, and NH 3 -and CO 2 -temperature programmed desorption. The influence of P−OH intensity and acid strength on activity was obtained through systematic studies over the formation process of VPO phases and the acidity distribution. Preparation and reaction parameters were investigated and optimized.