Dephlegmators can be used to reduce power consumption in low temperature gas separation processes. Most existing models have focused on separation process simulation, while the heat exchange characteristics and the refrigeration design were either ignored or based on highly simplified assumptions. This paper presents a new framework for the design of dephlegmators that addresses simulation of multicomponent partial condensation, design of plate-fin heat exchangers (PFHEs) and design of the refrigeration processes that service the dephlegmator. For simulation, a film model is applied to estimate local mass and heat transfer and integration across the separation area. In the design of PFHEs, the key issue is to determine the controlling stream according to the flow pattern in the separation passages. Design of refrigeration focuses on the optimization of the composition when mixed refrigerants are used, and on partition temperature when cascade cycles are used. A systematic methodology is proposed to include all these aspects. Various cases are studied to provide Guidelines in the design of dephlegmators used for multicomponent gas mixtures with different refrigeration systems.