This work aimed to investigate a typical bioethanol distillation process considering an alcoholic wine with 19 components and to validate the simulation results against experimental data collected from a Brazilian sugar mill. The process was investigated in terms of bioethanol alcoholic graduation, ethanol recovery, energy consumption and ethanol loss. Two optimizing approaches were tested: the central composite design (CCD) and the sequential quadratic programming (SQP). Both approaches allowed the optimization of the equipment configuration used nowadays and provided similar optimal conditions. The results showed that the simulation approach was capable of correctly reproducing a real plant of bioethanol distillation and that the optimal conditions guaranteed the bioethanol production according to legislation, with low consumption of steam and high recovery of ethanol. On the other hand, substantial fluctuations in wine composition may require adjustments of operational conditions or the use of specific control loops to prevent an off-specification product. (c) 2012 Elsevier Ltd. All rights reserved.