The solubility of lamotrigine (LTG) are measured in aqueous mixtures of carbitol at temperatures ranging from 293.2 to 313.2 K. LTG solubility increases with increasing mass fraction of carbitol, and maximum solubility is observed in neat carbitol. Four cosolvency mathematical models; i.e., Yalkowsky model, Jouyban–Acree model, Jouyban–Acree–van’t Hoff model and modified Wilson model are fitted to the experimental results, and back-calculation is performed by using the solubility data in monosolvents in which the mean relative deviation of the investigated models are 64.8%, 9.0%, 7.2%, and 46.7%, respectively. Furthermore, the apparent thermodynamic properties of the dissolution process are computed according to van’t Hoff and Gibbs equations. The preferential solvation is analyzed based on the inverse Kirkwood-Buff integrals by using the solubility values at 298.2 K. LTG is preferentially solvated by water in water-rich mixtures (0.00 < x₁ < 0.12) and by carbitol in mixtures with solvent composition of 0.12 < x₁ < 1.00.