Substantial quantities of energy are required in conventional distillation columns applied in high-purity separation of close-boiling mixtures. To achieve energy saving of distillation, a novel different pressure thermally coupled distillation (DPTCD) was proposed for separating the close-boiling mixture of n-butanol and iso-butanol. Both this intensified energy integration technique and two other processes, namely conventional distillation (CD) and vapor recompression column (VRC), were simulated in process simulator Aspen Plus. The optimization was carried out to determine the optimal values of design and operating variables on the basis of minimizing energy consumption. Subsequently, the energy saving and economic efficiency of the DPTCD scheme were evaluated through the comparison with the other two processes. The results showed that, compared to the CD and VRC processes, the energy consumption of DPTCD process was decreased by 65.21 and 15.79%, respectively, and the total annual cost (TAC) of DPTCD process can be reduced by 33.75 and 10.46%. It demonstrated that DPTCD scheme was the most promising alternative to reduce the total energy consumption and TAC with high purity (99.1 wt%) n-butanol and iso-butanol products among these separation processes.