A simulation study was performed for a two-phase partitioning bioreactor (TPPB) with polymer beads, Dowex Optipore L-493, as a second phase. When the initial glucose concentration is less than 30 g/L, a single-phase bioreactor is preferred, because it consumed all the glucose with 40% of biobutanol yield. Any glucose over the concentration remained in the single-phase bioreactor because cells were completely inhibited by products, mainly biobutanol, and thus glucose availability became less than 100%. The TPPB with 10% polymer beads completely consumed up to 120 g/L glucose and more polymer beads were required for the higher glucose concentration. Instead of increasing the proportion of polymer beads, 2 vvm of nitrogen gas was introduced continuously into the TPPB for the stripping of products, reducing product inhibitions. By applying gas stripping to the TPPB containing 10% polymer beads, 150 g/L of glucose was completely consumed and 99.7% acetone, 46.8% butanol and 82.5% ethanol was stripped out of the TPPB. Finally, on the basis of these estimations, a novel strategy based on the initial glucose concentration was suggested for high biobutanol production.