The temperature-composition cascade strategy was proposed to control the reactive distillation (RD) process for the synthesis of tert-amyl ethyl ether. Aspen Split tool was adopted to obtain the design parameters of the column from the viewpoint of separating tert-amyl alcohol, ethanol, and water. The proposed procedure which included optimization and sensitivity analysis was implemented to optimize the design parameters of the column and obtain the sensitive variables simultaneously, without requirement to run various simulations. In those optimized conditions, the proposed control strategy was introduced to manage the RD process by changing the sensitive variables. From results of the dynamic simulation, it can be known that the proposed strategy was able to handle disturbances while maintain the tert-amyl ethyl ether product purity and quickly reach the steady state. Therefore, the proposed control strategy was regarded as the effective control structure and could successfully control this RD system. (c) 2012 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.