This paper reports an experimental and computational thermochemical study on three barbituric acid derivatives: 1,3,5-trimethylbarbituric acid or (1,3,5-trimethyl-2,4,6(1H,3H,5H)pyrimidinetrione, CAS 7358-61-4), 1,5,5-trimethylbarbituric acid or (1,5,5-trimethyl-2,4,6(1H,3H,5H)pyrimidinetrione, CAS 702-47-6), and 1,3,5,5-tetramethylbarbituric acid or (1,3,5,5-tetramethyl-2,4,6(1H,3H,5H)pyrimidinetrione, CAS 13566-66-0). Values of standard (p0=0.1MPa) molar enthalpies of formation in the gas phase at T=298.15K have been derived from experiment. Energies of combustion were measured by static bomb combustion calorimetry and standard molar enthalpies of formation in the crystalline state at T=298.15K were calculated. Enthalpies of sublimation were derived from temperature dependence of vapour pressures measured by transpiration method. From these results, values of −(570.6±2.3), −(599.4±1.4), and −(605.1±2.9)kJ·mol−1 for the gas-phase enthalpies of formation at T=298.15K of 1,3,5-trimethylbarbituric acid, 1,5,5-trimethylbarbituric acid, and 1,3,5,5-tetramethylbarbituric acid, respectively, were determined. Theoretical calculations at the G3 and G4 levels were performed, and a study of the molecular and electronic structure of the compounds has been carried out. Calculated enthalpies of formation were in good agreement with the experimental values.