Abstract: The synthesis of isobutyraldehyde from methanol and ethanol was investigated over vanadium catalysts at 375℃ and under normal atmospheric pressure. The influence of V2O5 content and preparation conditions of catalysts on catalytic performances was studied. The results showed that 75% V2O5 content, 480℃ calcination temperature and 2h calcination time were the optimum conditions, and the ethanol conversion and isobutyraldehyde selectivity reached to 98.03% and 47.52% respectively. The fresh, reacted and regenerated catalysts were investigated by XRD and the reacted catalyst was also tested by DTATG to establish change of vanadium oxide. The results showed that V2O5 was reduced to V2O3 during reaction and deactivated catalyst could be regenerated.