Polysaccharide-based chiral columns were evaluated for the separation of enantiomers of four chiral epoxides under normal-phase and polar organic mode. Since all four studied compounds contain two centers of chirality and, thus, theoretically, the coexistence of four stereoisomers is possible, the columns were evaluated from the viewpoints of both, chemoselectivity and enantioselectivity. For two of the epoxides, enantioseparation was achieved in the normal-phase mode as well as in the polar organic mode on several polysaccharide columns. The polar organic mode is especially attractive for the preparative separation of the enantiomers due to the enhanced solubility of the compounds in these solvents, as well as due to a shorter run time. A new and unusual (stereoselective) peak focusing phenomenon was observed in some experiments.