Solubility determination of poorly water-soluble drugs is pivotal for formulation scientists when they want to develop a liquid formulation. Performing such a test with different ratios of cosolvents with water is time-consuming and costly. The scarcity of solubility data for poorly water-soluble drugs increases the importance of developing correlation and prediction equations for these mixtures. Therefore, the aim of the current research is to determine the solubility of acetylsalicylic acid in binary mixtures of ethanol+water at 25 and 37°C. Acetylsalicylic acid is non-stable in aqueous solutions and readily hydrolyze to salicylic acid. So, the solubility of acetylsalicylic acid is measured in ethanolic mixtures by HPLC to follow the concentration of produced salicylic acid as well. Moreover, the solubility of acetylsalicylic acid is modeled using different cosolvency equations. The measured solubility data were also predicted using PC-SAFT EOS model. DSC results ruled out any changes in the polymorphic form of acetylsalicylic acid after the solubility test, whereas XRPD results showed some changes in crystallinity of the precipitated acetylsalicylic acid after the solubility test. Fitting the solubility data to the different cosolvency models showed that the mean relative deviation percentage for the Jouyban-Acree model was less than 10.0% showing that this equation is able to obtain accurate solubility data for acetylsalicylic acid in mixtures of ethanol and water. Also, the predicted data with an average mean relative deviation percentage (MRD%) of less than 29.65% show the capability of the PC-SAFT model for predicting solubility data. A brief comparison of the solubilities of structurally related solutes to acetylsalicylic acid was also provided.