The problems of deactivation of iron oxide catalysts in the process of industrial dehydrogenation of methylbutenes to isoprene have been considered. The dependence of deactivation of the catalyst fixed bed on the time on-stream of different sections of the catalyst along the reactor height has been examined. The cause of poor performance of a part of the catalyst bed has been revealed and substantiated. Based of the results of the study, the authors propose an approach to predicting the catalyst performance during a long time on-stream.