The interest in n-butanol as a biofuel has increased in recent years because of its superior fuel qualities compared to ethanol: higher octane number, lower heat of vaporization, higher energy density (energy/volume), and lower vapor pressure. However, the concentration of n-butanol coming from the fermenter is lower than that achieved in ethanol fermentation. In addition, acetone and ethanol are also produced. Recent studies to improve yield and increase n-butanol concentration have explored fed-batch systems with stripping, adsorption, liquid-liquid extraction, distillation, and/or pervaporation to recover products. The production of n-butanol involves removing the acetone and ethanol and separating the n-butanol from the water. This separation is made difficult by the presence of an azeotrope. Fortunately, unlike the homogeneous azeotrope found in the ethanol/water system, the n-butanol/water azeotrope is heterogeneous; thus, two liquid phases occur in the decanter. Therefore, a simple two-column distillation system can be used. This paper studies the control of the n-butano/water azeotropic distillation system and develops a simple effective control structure that is capable of handling very large disturbances in throughput and feed composition. The control system is very robust and is demonstrated to be applicable for systems that are designed for a wide range of feed compositions.