This paper presents an economical design flowsheet and overall control strategy for simultaneous esterifications of ethanol and n-butanol mixtures with acetic acid. In this work, a difficult-to-design reactive-distillation (RD) process, classified as mixed Type-II/Type-III system, has been studied. After comparing three alternative design flowsheets, an indirect-sequence design containing a RD column, a top decanter, and a stripper gives significantly lower total annual cost and energy consumption than the other two designs. In the control strategy development, conventional inventory control with RD bottom level controlled by manipulating RD bottom flow shows that this process would exhibit multiple steady-states. An improved inventory control strategy with a rather unusual pairing by controlling this level using reboiler duty is proposed to alleviate this complex dynamic behavior. The dynamic results show that the proposed plant-wide control strategy is capable of holding product specifications despite disturbances from throughput and feed composition changes. (C) 2013 Elsevier Ltd. All rights reserved.