The equilibrium solubilities of chlorhexidine in four solvent mixtures of methanol (1) + water (2), ethanol (1) + water (2), DMF (1) + water (2) and 1,4-dioxane (1) + water (2) at temperature range from (278.15 to 318.15) K were reported. At the same composition of methanol, ethanol, DMF or 1,4-dioxane and temperature, the mole fraction solubility of chlorhexidine was highest in DMF (1) + w water (2) mixtures, and lowest in ethanol (1) + w water (2) mixtures. By using the Jouyban-Acree model, van't Hoff-JouybanAcree model and Apelblat-Jouyban-Acree model, chlorhexidine solubility was well correlated obtaining RAD lower than 1.69% and RMSD lower than 0.87 x 10 (4) . The dissolution process of chlorhexidine in solvent solutions was endothermic for the dissolution process. To study the solvent effect, solubility data were correlated to KAT parameters and cavity term on the basis of linear solvation energy relationships concept. Results indicate the key effect of cavity term and pi* in aqueous methanol and ethanol mixtures; cavity term in aqueous DMF mixtures; and cavity term, beta and pi* in aqueous 1,4-dioxan mixtures. Quantitative values for the local mole fraction of methanol (ethanol, DMF or 1,4-dioxane) and water around the chlorhexidine were computed by using the IKBI method applied to the determined solubility data. Chlorhexidine was preferentially solvated by water for the four solvent mixtures in water-rich compositions; while in intermediate and co-solvent-rich composition for ethanol (DMF, 1,4-dioxane) (1) + w water (2) mixtures, chlorhexidine is preferentially solvated by the co-solvent. The preferential solvation magnitude of chlorhexidine was highest in 1,4-dioxane mixtures than in the other three solvent mixtures. (C) 2018 Elsevier Ltd.