The minimization of the work consumption in a multistage membrane separation cascade operating in isoenthalpic conditions was investigated with regard to the splitting factor of each stage, for the assigned values of the number of stages, the retentate and permeate pressures, and the flow pattern. The mathematical model of the membrane separation cascade is presented, and five possible different flow patterns together with system variance are discussed. Under isoenthalpic conditions the work needs are due to the compression of the permeated stream, and the work losses to the generation of entropy on the mixing of recycled streams. A three-component mixture (NH3, H-2, N-2) and a polyethylene membrane were used as the standard testing system; the results of the optimization for three, five, seven, or nine stages cascades, using as the initial splitting factor values 0.5, 1.0, and 1.5 for all stages, are discussed. Increasing the number of stages increases the membrane surface area and the total work consumption owing to the increase in recycled stream flow. In the case under examination, both the efficiency index and the specific efficiency decrease for cascades of more than five stages. Therefore membrane staging seems to be unattractive from the point of view of both capital investment and operating costs, at least for more than a certain number of stages, depending on the specific problem.