Vinyl acetate monomer (VAM) is produced from oxidation of ethylene and acetic acid on a Pd-Au/SiO2 catalyst in the gaseous phase. A progressive loss in activity occurs during the lifetime of a commercial Pd-Au/SiO2 VAM synthesis catalyst; thus, the efficiency of the reaction decreases and the process is no longer operational and economically feasible. In this study, the effective parameters on Pd-Au/SiO2 catalyst deactivation were investigated using a fixed-bed reactor pilot, and a model was proposed to predict the reduction in catalyst activity. The proposed model's output was compared with experimental data and an acceptable agreement was observed. The error was <10%.