In this study, a dynamic model for a novel cascade membrane methanol reactor (CMMR) in the presence of long term catalyst deactivation was developed. In the first catalyst bed the synthesis gas partially convert to methanol. In the second reactor the reaction heat is used to preheat the feed gas to the first bed. The wall of the tubes in the both of reactors is covered with a palladium-silver membrane. The simulation results represent 4.7% and 3.92% enhancement in the yield of methanol production during 1400 days of operation in the CMMR in comparison with conventional dual type methanol reactor (CDMR) and membrane dual type methanol reactor (MDMR), respectively and a favorable profile of temperature and activity along the CMMR relative to MDMR and CDMR. Copyright (C) 2010 John Wiley & Sons, Ltd.