For the separations of the reacting mixtures with the most unexpected relative volatility order (i.e., the reactants feature the highest and lowest relative volatilities and the products the intermediate ones), feed splitting (FS) should be combined with top-bottom external recycle (TBER) in the design of reactive distillation columns with two reactive sections (RDC-TRS). Despite FS lessens the reactants with the highest and lowest relative volatilities flowing through the intermediate product extraction stage, the TBER is still effective to improve the contact of the reactants in the upper/lower reactive section and intensifies consequently internal mass and energy integration between the reaction operation and the separation operation involved. The design strategy is evaluated in terms of the separations of esterifications of lactic acid with methanol and palmitic acid with isopropanol. The simultaneous employment of FS and TBER is found to favor greatly system performance and the resultant process design is superior to those with one reactive section reinforced by a TBER and/or FS. These outcomes imply that the RDC-TRS with FS plus TBER should be the most competitive alternative for the separations of the reacting mixtures with the most unexpected relative volatility order. (C) 2016 Elsevier B.V. All rights reserved.