The statistical investigation and optimization of the characteristics of reactive distillation column for isoamyl acetate production to reduce energy consumption have been investigated using response surface methodology. Isoamyl acetate has three main applications including flavoring in the food industry, industrial solvent, and personal products. To optimize the characteristics of the reactive distillation, the variables under investigation included “Number of Reaction Stages” (2-4-6), “Number of Stripping Stages” (8-10-12), and “Number of Rectification Stages” (2-3). The response or dependent variables included “Reboiler Heat Duty” and “Condenser Heat Duty”. The response surface methodology and the CCD design method are used to model and determine the optimal levels of each parameter. The R2 value for “Reboiler Heat Duty” and “Condenser Heat Duty” are obtained at 0.9891 and 0.9890, respectively, indicating a high agreement of the model results with the input data. The optimal conditions included “Number of Reaction Stages”: 5, “Number of Stripping Stages”: 12, and “Number of Rectification Stages”: 2, in which “Reboiler Heat Duty” was 1737.107 W and “Condenser Heat Duty” was -1780.115 W. The simulation data matched the predicted responses of the statistical software, indicating that the statistical modeling is performed accurately.