A supercritical process for biodiesel fuel production is generally known to be less profitable than the alkali-catalyzed process due to high temperature and pressure requirements for the supercritical reaction. Only a few approaches have been proposed using experimental results to design a supercritical biodiesel process and to assess its profitability compared to the alkali-catalyzed process. In this study, a design for a supercritical biodiesel process was suggested and its economic performance with three different reaction conditions was simulated in the comparison with the conventional alkali-catalyzed process. It was found that the total capital cost was higher in all three cases of the supercritical process than in the alkali-catalyzed process due to the high cost of pumps, heaters, and heat exchangers. However, the total manufacturing cost of the supercritical process was lower than that of the alkali-catalyzed process due to the higher glycerol credit and the lack of a requirement for catalyst or solvent. The supercritical process can produce high-purity glycerol more easily that does not contain any water, which is unavoidable in the washing step of the alkali-catalyzed process. The higher steam cost in the supercritical process was compensated for by catalyst and solvent costs in the alkali-catalyzed process. Overall, one of the supercritical processes resulted in shorter payout time than the alkali-catalyzed process even when virgin oil was used as one of the raw materials, because the lower total manufacturing cost made up for the increased total capital cost.