In this study, we have searched optimized design and operating conditions of three reactive distillation structure for the esterification of acetic acid with ethanol to produce ethyl acetate and water. Effects of the distillate rate, feed location of the reactants, reflux ratio, and liquid holdup as design and operation variables on the performance of the reactive distillation were examined. Design and operation variables like these had different effects on the performance according to reaction type, feed location of the reactant, and distillation configuration. In the reaction type of A+B=C+D, when the reactants were not adjacent to middle components in relative volatility, conversion had an optimum point for distillate rate and reflux ratio. However, there was no optimum point in conversion when reactants were adjacent middle components. When the reactant was fed by split mode, the performance was less sensitive to the change of these variables than the other schemes. We here present guidelines for the optimum operating condition and the best scheme for the reactive distillation process.