A factorial design methodology was applied to the design of a dividing wall column, solving the complex multivariable problems and simultaneously optimizing the interacting variables to achieve the best design with respect to total annual cost. Column structure was practically optimized with a minimum of simulation runs. The proposed design method was tested in the design and optimization of an NGL recovery system; it allowed interactions between variables to be identified and quantified. The column system designed by the proposed method reduced reboiler energy consumption and total annual cost by 28.23% and 25.49%, respectively, in case 1, and those by 25.63% and 18.85%, respectively, over conventional distillation in case 2.