According to literature, ibrutinib (IBR) is a practically insoluble drug in water. The practically insoluble nature of IBR creates several problems in dosage form design of IBR. Hence, in this work, the thermodynamics of solubility of IBR in various ethanol + water cosolvent mixtures was studied. The solubility of crystalline IBR was determined at T = (298.15 to 323.15) and p = 0.1 MPa using an isothermal method. The measured solubility data of crystalline IBR were correlated well with three semiempirical models namely Van't Hoff, the modified Apelblat and Yalkowsky models. The solubility of crystalline IBR was observed highest in pure ethanol (mole fraction solubility: 3.12 × 10−3 at T = 298.15 K) and lowest in pure water (mole fraction solubility: 1.42 × 10−7 at T = 298.15 K) over the entire temperature range investigated. Thermodynamic parameters of crystalline IBR were determined by Van't Hoff and Krug et al. analysis and results indicated an endothermic, spontaneous and an entropy-driven dissolution of crystalline IBR in all ethanol + water cosolvent mixtures.