In this paper an improved method for studying processes for separation of multicomponent mixtures is presented. A thermodynamically oriented procedure was developed for the analysis and synthesis of the best heat-integrated distillation system. Systematic ranking of possible schemes was used in order to verify the best structure of a heat-integrated distillation system. An integrability criterion was introduced for the selection of the most promising heat-integrated sequences. Distillation columns were studied according to their ability for heat integration. The proposed selection of possible distillation columns sequences using rising integrability criteria gave a good approximation of the best heat-integrated distillation column sequences according to their total annual cost. Computational simulation of the process and pinch analysis were used for thermodynamic optimization of energy consumption. The method is illustrated with five- and six-component example problems.