Abstract: OBJECTIVE To prepare four polymorphs(Form I, Form III, Form IV and Form S) related in industry process of posaconazole and to study their relative stability and the phase diagram in methanol-water system. METHODS Solution crystallization method were chosen to produce the forms through controlling solvents, temperature and other crystallization conditons. XRPD, DSC, TGA were used to characterize polymorphs. Competitive ripening were taken to study the relative stability in methanol-water system. RESULTS In methanol-water system, water activity and temperature were both key parameters for crystal controlling. Higher water activity and lower temperature were conducive to Form IV; higher concentration of methanol and lower temperature were conducive to Form III; higher water activity and higher temperature were conducive to Form S; lower water activity and higher temperature were conducive to Form I. CONCLUSION Posaconazole has the risk of crystal form transformation in the crystallization process of the raw material drug and the formulation process of the formulation, and the risk of wet granulation in the formulation process is relatively high. Therefore, determining the preferred range of methanol for crystallization and washing during the crystallization process, is useful for the crystal form control in the drug substance and formulation manufactural processes.