The naftopidil solubility in aqueous co-solvent mixtures of n-propanol, ethanol, isopropanol and dimethyl sulfoxide (DMSO) at temperatures from 278.15 K to 318.15 K was reported. At fixed composition of n-propanol, ethanol, isopropanol or DMSO and temperature, the mole fraction solubility of naftopidil was highest in DMSO (1) + water (2) mixture, and lowest in isopropanol (1) + water (2) mixture. The Jouyban-Acree model and van't Hoff-Jouyban-Acree model provided well correlation results obtaining relative average deviation lower than 2.85% and root-mean-square deviation lower than 8.89 x 10(-4). Furthermore, the method of linear solvation energy relationships was performed with a suitable combination of solvent polarity descriptors to elucidate the nature of intermolecular interactions giving rise to the solubility variation in co-solvent mixtures. Quantitative values for the local mole fraction of n-propanol (ethanol, isopropanol or DMSO) and water around the naftopidil were computed by using the Inverse Kirkwood-Buff integrals method applied to the determined solubility data. Naftopidil was preferentially solvated by water for the four solvent mixtures in water-rich compositions; while in intermediate and co-solvent-rich compositions for n-propanol (isopropanol and ethanol) (1) + water (2) mixtures, naftopidil was preferentially solvated by the co-solvent. The preferential solvation magnitude of naftopidil was highest in isopropanol mixtures than in the other three co-solvent mixtures. (C) 2019 Elsevier Ltd.