Mixtures of supercritical CO2 and acetone are very often involved in supercritical fluid applications, and their thermodynamic properties are required to understand and design these processes. Excess molar enthalpies (H-m(E)) for CO2 + acetone mixtures were measured using an isothermal high-pressure flow calorimeter under conditions of temperature and pressure typically used in supercritical processes: pressures from (9.00 to 18.00) MPa and temperatures from (313.15 to 333.15) K. Mixtures showed exothermic mixing; excess molar enthalpies exhibited a minimum in the CO2-rich region. The effects of pressure and temperature on the excess molar enthalpy of CO2 + acetone are large. The most exothermic H-m(E), values were observed for a coincident CO2 mole fraction value of 0.771 at (323.15 and 333.15) K and 9.00 MPa: (-4176 and 4366) J.mol(-1), respectively. Two-phase vapor liquid CO2-rich regions are observed at (323.15 and 333.15) K and 9.00 MPa where H-m(E), linearly varies with CO2 mole fraction. For a given mole fraction and temperature, mixtures become more exothermic as pressure decreases. These trends were analyzed in terms of molecular interactions, phase equilibria, density, and critical parameters previously reported for CO2 + acetone. Excess molar enthalpies here reported were correlated using the Peng-Robinson equation of state and the classical mixing rule with two binary interaction parameters. The influence of the thermal effects on the phase behavior of CO2 + acetone mixtures formed in supercritical antisolvent precipitation experiments was discussed.