Previous studies have shown that hybrid distillation processes using either pervaporation or vapor permeation can be very attractive for the separation of mixtures. In this paper, a comparison between these two hybrid processes has been made. A tool has been presented that can assist designers and engineers to decide which process is more convenient for a specific application. Water removal from acetonitrile has been used as an example. A hybrid process with vapor permeation is preferred when the membrane is used either for water removal at high water concentration or just for overcoming the azeotropic composition. When the membrane removes water at water concentrations lower than the azeotropic point, pervaporation is more effective. Recycling part of the product as permeate (product sweep) and applying different pressures in the distillation columns and the membrane unit strongly reduce the required membrane area and the total cost of the process. Relatively low membrane selectivities are required for an economically optimal hybrid membrane-distillation process.