Abstract: Baicalein-nicotinamide(BE-NCT)co-crystal was chosen as model drug to investigate the thermodynamic characteristics. Solubilities of BE in NCT solutions in ethyl acetate at different temperatures were determined in order to explain the complexation behavior of BE-NCT co-crystal. Thermodynamic parameters of co-crystal formation progress were calculated. Ternary phase diagrams(TPDs)of the BE-NCT-ethyl acetate systems at various temperatures were established. The non-linear fitting equation according to 1 ∶1 complexation mechanism of BE-NCT co-crystal demonstrated a good correlation between calculated and experimental data(R²> 0. 98). Co-crystal formation is a spontaneous process(ΔG°< 0). Increase in temperature resulted in the increase of K_sp, decrease of K11 and a narrowed co-crystal zone. The degree of spontaneous reaction also decreased with increased temperature. The spontaneous reaction no longer carried out if the temperature reached T^*=315 K since ΔG°=0(ΔH°=-6. 314×10^-2 kJ/mol, ΔS°=-0. 200 5 J/mol ·K). A drop in temperature favors the complexation between BE and NCT in ethyl acetate. Since NCT has higher solubility than BE in ethyl acetate, the TPDs of co-crystal was asymmetric. The DSC diagrams of products prepared via three presupposed methods confirmed that the BE-NCT co-crystal could be generated in solutions of nonstoichiometric compositions.