We investigated the cause of a difference in the crystallization aspect depending on a surface area-increasing material (ion exchange resin) in the vancomycin crystallization process with increased surface area per volume of reaction solution (S/V). The result in terms of whether or not crystallization occurred was reversed when the ionic form of the ion exchange resin was altered. In addition, it was shown that the pH range of a solution for vancomycin crystallization was 4-7. Eventually, it was confirmed that vancomycin crystallization was affected by a change in pH of a crystallization solution depending on the ionic form of the ion exchange resin. Furthermore, in the absence of ion exchange resin, the time required for crystallization increased as the pH rose from 4-7. In addition, the size of the vancomycin crystal increased as the pH decreased.