Enthalpy of formation values for 1:1 carbamazepine:saccharin (CBZ:SAC), cyheptamide:saccharin (CYH:SAC), and 10,11-dihydrocarbmazepine:saccharin (HCBZ:SAC) co-crystals and relative enthalpy differences between polymorphs of the co-crystal formers - CBZ(P21/c, P1̄), CYH (P21/c, P1̄), and HCBZ (P21/c, Pbca) - were calculated from enthalpy of solution measurements. The results showed that the co-crystals were enthalpically stabilized and the more stable polymorphs of the co-formers were CBZ-P21/c, CYH-P21/c, and HCBZ-Pbca. The differences in enthalpies between polymorphs were related to the differences in the packing of the molecules. Likewise, the heats of formation of the co-crystals were related to differences in molecular and crystal structures. The transfer enthalpies for the components were assessed and included in the enthalpy of formation calculation. The free energy of formation of CBZ:SAC calculated from the ternary CBZ-SAC-methanol phase diagram showed that the co-crystal was the stable thermodynamic form, and the kinetics of crystallization followed the thermodynamics of crystallization. © 2010 American Chemical Society.