Oxygen scavenger applications in flexible food packaging are still limited due to the difficulty to ensure scavenging activity during storage and throughout the product shelf life. To avoid fast inactivation of the scavenger, multilayer active structures can be realized by inserting the active layer between two or more inert layers. In this work, an unsteady-state 1D reaction-diffusion mass transfer model was developed for predicting and optimizing the barrier-to-oxygen performance and the physical configurations of the co-extruded multilayer active films. The film configuration was a three-layers structure composed of polyethylene terephthalate (PET) as external inert layers, and PET with a polymeric oxygen scavenger as the core reactive layer. Scavenging activity of the multilayer film increased with the reactive layer thickness. Oxygen absorption reaction at short times decreased proportionally with the thickness of the external layers. The most appropriate combinations of inert-to-active film thickness were studied and analyzed. (C) 2017 American Institute of Chemical Engineers.