The solubility of nimodipine (NMD) in several PEG 400 + ethanol mixtures was determined at five temperatures from 293.15 to 313.15 K. The thermodynamic functions of Gibbs energy, enthalpy and entropy of solution and of mixing were obtained by using the van't Hoff and Gibbs equations from these solubility data and drug properties of fusion. The highest solubility value was obtained in PEG 400 and the lowest in ethanol at all temperatures. A non-linear enthalpy–entropy relationship was observed from a plotof enthalpy vs. Gibbs energy of solution. Accordingly, the driving mechanism for NMD solubility in ethanol-rich mixtures is the enthalpy, whereas in PEG 400-rich mixtures thedriving mechanism is the entropy, although the molecular events involved are unclear.