In this work, we investigated the deactivation of a commercial ZSM-5 based catalyst during ex situ catalytic fast pyrolysis (CFP). The experimental runs were carried out in a novel cascade dual fluidized bed reactor system where thermal pyrolysis of biomass was carried out in the first reactor, while ex situ catalytic conversion of the pyrolysis vapours was carried out in the second reactor. Consecutive reaction-regeneration cycles were realised using the same catalyst batch in order to evaluate catalyst deactivation over time. A comparison between in situ and ex situ CFP revealed that in contrast to what was observed in the case of in situ CFP, no accumulation of biomass-derived metals on the catalyst was observed during ex situ CFP. Both acidity and surface area were less affected compared to in situ CFP and the catalyst maintained higher activity. Product distribution and composition exhibited some variation over time which was attributed to the accumulation of biomass ash in the pyrolysis reactor and not to the poisoning of the catalyst bed. These results clearly demonstrated that ex situ CFP is an effective way to avoid catalyst poisoning during the CFP of biomass and to prolong catalyst lifetime.