We systematically examined the effect of the solvent system (methanol/water or acetone/pentane) on precipitation characteristics and mechanisms in the increased surface area precipitation (ISAP) with different ion exchange resins for the purification of paclitaxel. When Amberlite IRA 400Cl was added to increase the surface area, the acetone/pentane system was found to be more effective than the methanol/water system in terms of paclitaxel purity. The addition of surface area-increasing materials increased the yield in the methanol/water system, whereas it decreased the yield in the acetone/pentane system. Precipitates in the methanol/water system were needle-shaped or star-shaped, spreading from the central nucleus along the growing branches, while precipitates in the acetone/pentane system were disk shaped, branching out from around the nucleus. When Amberlite IRA 400Cl was added, it was possible to obtain smaller paclitaxel precipitates in the acetone/pentane system than in the methanol/water system.