A supercritical biodiesel production process via transesterification of vegetable oil with methanol, using CO2 as co-solvent is designed, simulated, and validated with experimental data. A preliminary study of the liquid-vapor equilibrium of the reacting mixture at different compositions was done to determine the supercritical conditions, by means of pressure-temperature diagrams. Under supercritical conditions, the presence of a single phase increases the reaction kinetics, avoiding the limitation by interphase mass transfer, and enabling to carry out the process with low residence time. The proposed process is based on two fixed-bed catalytic reactors in series, with intermediate glycerol separation. CO2 used as co-solvent decreases the critical temperature, enabling to carry out the process in milder conditions. The intermediate glycerol separation displaces the chemical equilibrium towards higher conversion of triglyceride, increasing biodiesel yield. The results of a complete experimental study are used to validate the model, through a comparison with the simulations result. (C) 2017 Elsevier B.V. All rights reserved.