The process design and control of the transesterification of methyl acetate and n-butanol by reactive distillation (RD) to produce methanol and n-butyl acetate are investigated in the study. The products from the RD column include n-butyl acetate and a methanol/methyl acetate mixture, which is separated by an additional separation column. In the study, the transesterification RD process with thermal coupling is redesigned from a previous paper. An innovative process, heat-integrated RD, which combines RD and heat-integrated distillation, is also designed to produce high-purity products of the reaction. The heat-integrated RD process provides the best energy efficiency. Proper selection and pairing of controlled and manipulated variables chosen for three control objectives were determined by using steady-state analysis for the heat-integrated RD process. A simple temperature control scheme is sufficient to maintain product purities and stoichiometric balance between the reactant feeds without resetting the set points of temperature loops.