Application of a heat pump system is a possibility for decreasing the high energy demand of distillation. The use of different working fluids for a vapor compression system for batch distillation is investigated. In this study working fluids are classified as wet and dry based on their behavior during the compression. The separation of a low relative volatility mixture (n-heptanetoluene) is investigated by rigorous simulation performed with a professional flow-sheet simulator. Standard reactor-reboiler is applied and simulated in a rigorous way (including the conditions of heat transfer). The basic criteria for the selection of the possible working fluids are determined. Based on these criteria n-hexane, n-pentane, ethanol, and isopropyl alcohol are studied as working fluids. The effectiveness of different working fluids is compared. The effect of the main operational parameters on the length of the payback period is examined. The minimal payback time is determined for the different working fluids. The best results are obtained for n-hexane.