We investigated the effects of ion exchange resins on the efficiency of crystallization with an increased surface area for the purification of vancomycin. As surface area-increasing materials, diverse types of ion exchange resin were used to increase the surface area per working volume (S/V). When the S/V was increased, in cation exchange resin Amberlite 200, Amberlite IR 120 (Na), and Amberlite IRC 50 and in anion exchange resin Amberlite IRA 400 (Cl) and Amberlite IRA 910 (Cl), vancomycin crystals were successfully generated. The yield of vancomycin increased (>97%), and the time necessary for crystallization was reduced dramatically (reduced from 24 hr to 12 hr). On the other hand, the purity of the vancomycin was approximately 95% and was not affected by increasing S/V. Use of an ion exchange resin also resulted in the production of smaller vancomycin crystals than in the absence of ion exchange resin.