Alternatives for the separation of three-component zeotropic mixtures are compared using simulation optimization with the total annual cost as the objective function. Conventional two-column sequences with and without column stacking are compared with three types of dividing-wall columns (DWCs). All processes are modeled with a rigorous process simulator and optimized using simulated annealing. The results are represented using ternary maps and used to regress parameters of a model that predicts the relative cost of process alternatives as a function of the feed composition, relative volatilities, and ease of separation index. The results highlight the importance of considering column stacking when choosing a process alternative for the ternary separation: in some cases, the region where the stacked two-column configuration is preferable to a dividing-wall column is significantly larger than the area where a conventional two-column configuration is preferable to a dividing-wall column.