Abstract Reactive separation technologies were proposed recently for fatty acid methyl esters (FAME) production, providing significant benefits such as minimal capital and operating cost savings. One approach is to use a reactive dividing-wall column (R-DWC) for the biodiesel production process. However, since the R-DWC is designed for a quaternary reactive system – two reactants (one in excess) and two products – more difficulties concerning the process control may be expected considering the high degree of integration of the process. This study is among the first to tackle the optimal design, dynamics and control of such an integrated unit and proposes an efficient control structure for a biodiesel process based on reactive DWC technology. AspenTech Aspen Plus and Aspen Dynamics were used as computer aided process engineering (CAPE) tools to perform the rigorous steady-state and dynamic simulations, as well as the optimization of the new R-DWC based biodiesel process. A key finding of this study is that it is imperative to use a vapor feed of alcohol in order to reach the product specifications. Singular value decomposition (SVD) was used to determine the sensitive trays for inferential temperature control. The control structure proposed here demonstrates the excellent performance of the system in the case of industrially relevant disturbances such as production rate changes or catalyst deactivation.