Design and optimization procedures employing the response surface methodology (RSM) for retrofitting the conventional extractive distillation sequence to a thermally coupled extractive distillation scheme (TCEDS-SR) is presented. The optimum TCEDS-SR structure can be found in a practical manner with minimal simulation runs. Furthermore, the RSM allows the interactions between variables to be identified and quantified. The separation of close boiling point mixtures and azeotropic mixtures was examined to test the proposed method. The predictions agreed well with the results of a rigorous simulation. The results showed that a retrofit of the extractive distillation sequence to TCED-SR can achieve significant energy savings compared to the conventional extractive distillation sequence. (C) 2012 American Institute of Chemical Engineers AIChE J, 59: 1175-1182, 2013