Two objective functions representing the second-law efficiency and the operating cost in binary distillation operation were empirically derived and used to optimise the operations of the distillation column. The benzene-toluene and the methanol-water mixtures, process simulation, exergy analysis, operating cost analysis, statistical design of experiments and optimisation were employed in the study. The results showed that the optimum operating set points for the operating variables in the distillation column – feed temperature, column pressure and feed flow rate – were the same for the exergetic and operating cost objective functions. An increase in second-law efficiency corresponded with a decrease in operating cost for the two binary mixtures considered. This implied that the optimisation study using the exergetic objective function is meaningful and realistic.