A reactive-extractive distillation (RED) combines the beneficial features of both reactive and extractive distillations in one column and relies on the reaction heat for the subsequent separation process to improve the energy efficiency. Here, a double-column RED with a preconcentration column (i.e., a threecolumn process) is proposed to replace the original conventional extractive distillation (CED) with a preconcentration column (i.e., a four-column process) for the recovery of diisopropyl ether and isopropyl alcohol from wastewater. First, the proposed process is conceptually designed to meet all product specifications. Then, the initial design is optimized using particle swarm optimization (PSO) with minimum total annual cost (TAC) as the objective. This is followed by exploration of three different feed-effluent heat exchanger (FEHE) configurations as a heat-integration (HI) strategy for energy conservation. Our results revealed that the optimized process with two FEHEs (case 3) provides significant improvement in TAC, energy consumption, environmental emissions, and thermodynamic efficiency by about 42, 57, 57, and 9%, respectively, as compared to the base case.Article pubs.acs.org/IECR