A three-phase nonequilibrium model developed recently in our laboratory was used to provide the optimal design and operating conditions of a catalytic distillation (CD) column for the aldol condensation of acetone. The influence of reflux flow rate, reflux ratio, reaction temperature, feed location, catalyst packing height, packed height of the nonreactive zones, reaction zone location, amount of catalyst, feed rate, and mass transfer on the conversion and product selectivity was investigated. The analysis and graphical representations were used to provide the optimal design and operating conditions of the CD column. Results obtained from our pilot CD column for the production of diacetone alcohol using Amberlite IRA-900 as a catalyst are in excellent agreement with the model predictions. This illustrates that this three-phase nonequilibrium model is effective for design, and this systematic modeling methodology can be used to provide the optimal design and operation parameters of a CD process.