AbstractMathematical formulation was made for the performance evaluation of extractive fermentation using multiple solvents. Two types of solvent‐supplying strategies were considered. One is to add multiple solvents simultaneously and the product is removed at one time. Another is to add them one by one consecutively. Computer simulation was made for batch, fed‐batch, and repeated fed‐batch operation of acetone–butanol fermentation to show the power of the approach. The result shows that the significant performance improvement in terms of the productivity and the product concentration is expected when two extractants such as oleyl alcohol and benzyl benzoate are used as compared with the case of using only one solvent.