Optimum experimental conditions and column design parameters are calculated for most economical separation of binary mixtures by preparative liquid chromatography. The solvent consumption and capital costs are regarded as the two major cost contributions. Calculations were performed by using the numerical solution of the equilibrium-dispersive model of chromatography and a nonlinear simplex algorithm. Solvent consumption depends only on the column efficiency, the retention factor, and the loa&ng factor. The production rate depends on the particle size, the column length, the mobile-phase flow velocity, the retention and the loading factors, and can be optimized with or without recovery yield constraints. A hybrid objective function was constructed to find the tradeoffs between the production rate and the solvent consumption.