A ternary separation usually requires the use of two simulated moving bed (SMB) units in series. Since an increase in the number of SMB units leads to a significant increase in capital and operational costs, the use of a single SMB unit is preferred if its structure can be modified to treat a ternary separation. Such a modified single SMB unit has been typified by a five-zone SMB or a two-zone SMB so far. The separation performances of a five-zone SMB and a two-zone SMB are compared in this paper by using the ternary amino acid mixture as a model system. A five-zone SMB is designed with the safety margin method while a two-zone SMB is optimized using genetic algorithm. A five-zone SMB based on the maximum allowable safety margin, although it may not guarantee the global optimum solution, results in much better separation performance than a two-zone SMB at its global optimum state.