Separating close-boiling components using distillation is very common in industry: Considering the higher capital and energy intensity of the task, schematic selection of optimal distillation strategies becomes a significant decision of both industrial and methodological importance. In this sense, this paper introduces a reliable shortcut method of simplicity and robustness for optimizing the target of total annualized cost (TAC). In detail, selective analyses are carried out among four schematic candidates for three close-boiling systems. The schemes are conventional distillation column, mechanical vapor recompression (MVR), double-effect distillation, and distillation with a recycle process. The mixtures to be separated are methyltrichlorosilane/dimethylchlorosilane, methylcyclopentane/cyclohexane, and isobutanol/n-butanol. After the first round evaluation, hydraulic calculations through rigorous simulations are worked out to size the equipment, which is necessary for TAC analyses. In the second round comparison, MVR stands out to be a more attractive option for close-boiling separations than other configurations.