This study was aimed at comprehensively analyzing the exergoeconomic and exergoenvironmental performance of a continuous reactor applied to synthesize fuel additive (acetins) by glycerol esterification with acetic acid in the presence of Amberlyst 36 catalyst. The effects of various process parameters viz. esterification temperature, acetic acid/glycerol molar ratio, and reaction pressure on both exergoeconomic and exergoenvironmental variables were studied at a constant feed flow rate of 0.5 mL/min. In addition, an optimization study was conducted using response surface methodology (RSM) through minimizing both cost and environmental impact per exergy unit of the product. Overall, both acetic acid/glycerol molar ratio and esterification temperature had profound effects on the variables of both exergy-based methods, while reaction pressure trivially affected the output parameters. The optimum operating conditions were: acetic acid/glycerol molar ratio = 1.1:1, esterification temperature = 102.0 degrees C, and reaction pressure = 16.7 bar. Under these conditions, the cost and environmental impact per exergy unit of the product were found to be 218.11 USD/GJ and 171.40 mPts/GJ, respectively. Generally, noticeable differences were observed in the optimum operating conditions proposed based on the process yield compared with those suggested by the exergoeconomic and exergoenvironmental methods.