The preferential solvation parameters (delta x(1,3)) of amiodarone hydrochloride (AMDH) in three binary solvent mixtures of ethanol (1) + water (2), N-methyl pyrrolidone (NMP) (1) + water (2) and propylene glycol (1) + water (2) were derived from their available solubility data by using the inverse Kirkwood-Buff integrals method. The values of delta x(1,3) varied non-linearly with the co-solvent (1) proportion in all the aqueous mixtures. For the system of ethanol + water, the values of delta x(1,3) were negative in water-rich mixtures and co-solvent-rich mixtures, but positive in intermediate compositions. However, for the propylene glycol (1) + water (2) mixtures with composition 0.167 < x(1) <1 and NMP (1) + water (2) mixtures with composition 0.20 < x(1) < 1, the delta x(1,3) values were positive indicating that AMDH is preferentially solvated by co-solvent. The positive delta x(1,3) values could be explained on the basis of the higher acidic behavior of AMDH molecules interacting with the hydrogen acceptor groups present in co-solvent. (C) 2017 Elsevier Ltd.