In this study, a new method to determine the solubility of crystalline drugs in (amorphous) polymers is proposed. The method utilizes annealing of supersaturated amorphous solid dispersions to achieve equilibrium between dissolved and recrystallized drug. By measuring the enthalpy of melting and mixing (H_m+mix) of the recrystallized drug, the equilibrium solubility of the drug in the polymer at the annealing temperature is determined. The equilibrium solubilities at these elevated temperatures were used to extrapolate to room temperature using the Flory-Huggins model. The new H_m+mix method showed solubility predictions in line with the melting point depression (MPD) and recrystallization (RC) methods for indomethacin (IMC) -polyvinylpyrrolidone (PVP). For IMC-hydroxypropyl methylcellulose (HPMC), the MPD method plateaued rapidly, leaving only one usable data point. The RC method showed large variations in the solubility predictions possibly due to a narrow glass transition temperature (T_g) window or inaccurate T_g determination. In contrast, the new H_m+mix method showed robust solubility prediction over the entire annealing temperature range with low variation and narrow error margins after extrapolation for both drug-polymer systems. The new H_m+mix method was able to accurately determine the drug-polymer solubility of IMC-HPMC, showing promise as a new tool to determine the solubility of problematic drug-polymer systems.