A semicontinuous two-zone SMB/chromatography hybrid system was designed for ternary separations, and compared to cascades with two two-zone SMBs and two four-zone SMBs. Operating conditions, productivity, and minimum D-total/F values were determined with the local equilibrium model, and purities were simulated using Aspen Chromatography version 11.1. Phenolic mixtures and sugar mixtures were used as models of moderately difficult and difficult linear separations, respectively. At the same productivity, the two-zone SMB/chromatography system gives at least 95% purities with reasonable D-total/F values and shows comparable performance with the two four-zone SMB cascade for the moderately difficult separation. For the difficult separation, the two-zone SMB/chromatography system has low purities with large D-total/F values, while the two four-zone SMB cascade gives higher purities at lower Dtotal/F values.