This work investigated for the first time a CO2 antisolvent crystallization (SAS) operating in non-isothermal conditions, i.e. injection of a solution warmer than that of the CO2 - in order to impose an additional driving for crystallization when CO2 was not a strong antisolvent The approach focused on phase equilibria (with a distinctive feature of being modeled by artificial neural network) and 3D-simulation of the mixing (considering both heat and mass transfers) in order to detail the supersaturation profiles in the mixing zone and confronted them to the crystallization results. The effect of pressure was investigated as well. The solubility of a model compound, mefenamic acid (MEFE) was measured in CO2-acetone at 35 degrees C/8.5, 10 and 15 MPa, and 10 MPa/25, 35 and 45 degrees C and further correlated by a neural network to provide an easy-to-handle equation of MEFE concentration. Simulations results showed that supersaturation levels were low (around 2) and that the expanding jet spread similarly whatever the pressure. The effect of differential temperature on the mixing behavior and supersaturation was investigated. Compared to isothermal cases, higher superaturations were obtained but only if a more concentrated solution allowed by the higher temperature was processed as well. The benefit for the crystal size was difficult to evidence because of the long sizes of the needles and the difficulties of processing almost saturated solutions. Investigation of a less CO2-acetone compound would be more promising. (C) 2013 Elsevier B.V. All rights reserved.