We evaluated the effects of the sample feeding and mixing methods on the efficiency of vancomycin crystallization and developed a method to dramatically shorten the time required for crystal formation by increasing the available surface area inside the reactor. The highest purity (97%) and yield (99%) of vancomycin could be obtained with an initial one-step feeding and mixing method, resulting in the formation and growth of spherical fan-shaped crystals. The yield of vancomycin increased when the surface area per working volume (S/V) was increased to 0.428 mm(-1) using glass beads (0.5 mm), the cation exchange resin Amberlite 200, or the anion exchange resin Amberlite IRA-400. In particular, most of the vancomycin (>99%) could be recovered after 6 h of crystallization using Amberlite 200, resulting in a dramatic reduction in the time required for crystallization. On the other hand. increasing S/V had almost no effect on vancomycin purity and crystal size. (C) 2011 Elsevier Ltd. All rights reserved.