The combination of a chemical reaction and a distillative separation in one apparatus shows several advantages compared to the separately performed processes. The present contribution presents a comparative study of several possible models of different complexity for this reactive distillation process. These models consider multiple chemical main and side reactions which are always present in the industrial production of the fuel ethers MTBE and TAME. Due to the strong nonideality of the reaction mixtures, liquid-phase activities are used for the formulation of the reaction kinetics. The simulated results were experimentally validated in two packed laboratory-scale columns. It can be shown that the consideration of side reactions and the modelling of internal catalyst phenomena play an important role for the interpretation of the experimental results. The comparison of a rate-based model and a Murphree equilibrium stage model shows that the latter one with a lower complexity yields equivalent model predictions for the MTBE-system.