Abstract: Synthesis of efficient cryogenic distillation sequence for purifications of natural gas having medium and high concentration of carbon dioxide content, has been explored in the present study. Calculations were performed for conventional and hybrid distillation column sequences by using the heuristic and evolutionary strategies. Different feed compositions were selected from literature and the possible sequence for different feed composition is computed. Three different sequences, namely direct, in-direct and mixed were chosen for each of the feed. Total minimum vapor flow and marginal vapor flow calculations were performed for each of the sequences. Capital and energy requirements were compared to show the advantage of hybrid network over conventional cryogenic network.