The aim of this study was to develop a thermodynamic model for a better understanding of glycerol esterification process with acetic acid in a continuous reactor. Response surface method (RSM) was also used to optimize the operating conditions of the reactor applied for synthesizing acetins from the exergetic viewpoint. The effects of reaction temperature (100-140 degrees C), feed flow rate (0.2-0.6 mL/min), acetic acid to glycerol molar ratio (1-3), and pressure (1-160 bar) on the exergetic performance parameters of the process were studied. The optimum operating conditions of the reactor were determined by maximizing universal and functional exergetic efficiencies and minimizing normalized exergy destruction, simultaneously. Overall, RSM predicted the exergetic performance parameters of the reactor with an R-2 higher than 0.98. Reaction temperature of 117 degrees C, feed flow rate of 0.6 mL/min, acetic acid to glycerol molar ratio of 1.1, and pressure of 1 bar yielding normalized exergy destruction of 3.1, universal exergetic efficiency of 37.5%, and functional exergetic efficiency of 20.8%, were found as the best operating conditions of the reactor. The results showed that, unlike exergy analysis, process yield (glycerol conversion) alone could not be a perfect performance metric in order to make decisions on the operating conditions of the reactor. The optimum operating conditions found in the current study could be applied at commercial scale for resource-efficient, cost-effective, and eco-friendly valorization of glycerol into acetins. (C) 2018 Elsevier Ltd. All rights reserved.