The synthetic production of butanol has completely substitute the original fermentation process where butanol, acetone and ethanol were simultaneously produced in the so called ABE process. As most of the bio-alcohols produced by fermentation, the dilution in water makes their separation challenging due to the presence of azeotropes. The bio-related process competitiveness, in economic terms, is mainly related in developing energy efficient separation alternatives to reach the market grade purity. Distillation, is one of the preferred separation technique, but it suffers of a low thermodynamic efficiency. Anyway, distillation still represents an efficient separation method if properly combined with other unit operations in hybrid flowsheets. In particular, in the present work, liquid-liquid extraction is considered to separate water from the fermentation broth. Then, the quaternary mixture composed by the extraction solvent, acetone, butanol and ethanol could be efficiently separated by distillation. First, the simple column configurations (SCCs) were designed and optimized minimizing the total annual cost, the eco-indicator 99 and the condition number as multi-objective function. The combined extraction-indirect configuration was selected as best SCC. Starting from this reference different ternary DWC arrangements were proposed. Among all the alternatives, it was obtained that, after the extraction, is more convenient to remove the solvent in a simple column and proceeds with the separation of acetone, ethanol and butanol in a DWC. For this arrangement the objective functions are lower compared to the hybrid extraction-simple indirect configuration. In particular, a remarkable 16% reduction in the total annualized cost was reached.