The Ethanol-water separation involves a well-known azeotrope that confines the achievement of the ethanol purity to the values higher than 95 wt% using straightforward distillation. Many attempts have been made to identify how it can be possible to produce ultra-pure ethanol (99.95 wt%) for various valuable applications. In practice, minimizing the total cost of the process is of high importance beside having the finished product with utmost purity. As a consequence, finding the best process conditions imposed to apply the simulation and statistical optimization methods in combination. Numerical optimization provides the best trade-offs to achieve the goals. In this research, the separation of the ethanol/water mixture (87 wt%) was simulated using azeotropic distillation in Aspen plus© environment. Indeed, cyclohexane was chosen as an effective azeotrope-former. The UNIQUAC equation was used to describe the phase behavior. The two-column arrangement, in which the first column was used to dehydrate ethanol and the second to recover the entrainer, was applied in this simulation. The effect of important process variables, including the number of the trays in columns and the feed-tray position in each tower on the total capital cost were investigated. Finally, the process variables were optimized via the Response Surface Methodology to minimize the total cost of the process. The results uncovered that the total capital cost would be minimized if the number of the trays in the azeotropic (C1) and recovery (C2) columns were set to 34 and 40, whereas, the feed-tray numbers were adjusted to 19 and 9 respectively
