Abstract: The aim of this study was to investigate the effect of polymers on the formation thermodynamics of adefovir dipifoxil(AD)-saccharin(SAC)cocrystal. In the absence and presence of polymers such as polyethylene glycol, ethyl cellulose, polyvinylpyrrolidone and Eudragit E100, solubilities of AD and SAC in ethanol solution containing different concentrations of SAC at variable temperatures were determined by high-performance liquid chromatography(HPLC). Appropriate mathematical model for the description of the influence of polymers and temperature on the solubility of AD-SAC cocrystal was established. The ternary phase diagrams were set up using the assayed solubilities data, and they were used to predict changes of cocrystals solubility and product yield. Addition of polymers resulted in increased solubility of AD-SAC cocrystal, decreased complexation constants(K₁₁), enhanced solubility products(K_sp), but there was a gradually decreased free energy change(ΔG⁰). The areas of homogeneous liquid phase and pure solid cocrystal in equilibrium with the liquid phase in ternary phase diagrams were also found to be larger. Therefore, although there was no change to the spontaneity of AD-SAC cocrystal formation, there existed retardation to cocrystal formation and reduction in product yield of pure cocrystal in the presence of polymers. Moreover, application of polymers could broaden the concentration range of AD and SAC solutions when solution crystallization was selected to prepare cocrystal.