On the basis of analyzing the azeotropic behavior, comparing the accuracy of different property models and selecting reaction kinetics, a reactive distillation (RD) process for production of isopropyl acetate (IPAc) through the esterification of acetic acid and isopropanol is designed, through which high-purity isopropyl acetate product can be obtained. Besides, considering the high energy requirements of the RD process, a different pressure thermally coupled reactive distillation (DPTCRD) process is proposed to reduce the energy expenditure. To check the feasibility of the DPTCRD process, the main parameters affecting the performance of the DPTCRD process are investigated and optimized, during which the product purity is specified to meet the requirement, finally, the total annual cost (TAC) is calculated. It is verified that the activity coefficient model NRTL-HOC can be successfully employed to describe the liquid and vapor behaviors, and the DPTCRD process is feasible and economical in obtaining the high-purity IPAc product with a lower total annual cost.