In this paper, two novel polymorphs of adefovir dipivoxil-saccharin (AD-SAC) cocrystals, forms II and III, were prepared and characterized by PXRD, DSC, FT-IR and SEM. Polymorphic transformations of these two forms and the known form (form I) were also investigated. In comparison to form I, forms II and III of AD-SAC cocrystals showed different thermal behaviors on DSC, characteristic diffraction peaks on PXRD and absorption spectra on FT-IR. In addition, form I exhibited an irregular plate-like shape, while forms II and III showed as needle-like shape and stubby columnar shape, respectively. During the heating process on DSC, forms I and II underwent solid-solid transformations to form III with endothermic transition peaks, suggesting that forms I and II were enantiotropically related to form III. Furthermore, slurry conversion experiments in ethanol showed forms II and III would quickly convert to form I by solution-mediated transformation, indicating that form I was the most stable form among three forms of AD-SAC cocrystal from 15 to 50 °C.