The solubility of lamotrigine (LTG) was reported in full concentration range of acetonitrile + water at T = 293.15–313.15 K. The solubility data were correlated by the Jouyban-Acree, Jouyban-Acree-van’t Hoff, NRTL, UNIQUAC and Wilson equations in addition to modified Wilson and Machatha. With respect to the obtained %ARDs, Jouyban-Acree is superior to Jouyban-Acree-van’t Hoff and the order of %ARDs for non-linear models is NRTL < UNIQUAC < Wilson. Moreover, the Machatha non-linear is more consistent with experimental data rather than modified Wilson for correlating the data with regard to the solvent composition. Finally, apparent standard Gibbs energy, enthalpy and entropy of dissolution and mixing, ΔGsoln∘, ΔHsoln∘, ΔSsoln∘, ΔGmix∘, ΔHmix∘, ΔSmix∘ of LTG in aqueous mixtures of acetonitrile were computed at mean harmonic temperature Thm = 303.0 K. The positive variable of ΔGsoln∘ suggesting the favourability of dissolution in acetonitrile-rich mixtures and ‘entropy-driven’ nature of it in only four cases.