The most outstanding feature of batch distillation is its flexibility in design and operation. In particular, when chemical reactions and physical separations have some overlapping operating conditions the combination of these tasks in a single process unit can offer significant benefits. In this work, the optimal operation of a new operation mode for reactive batch distillation in middle vessel columns is presented. By this means, the efficiency of reactive batch distillation can be improved, e.g., less batch time and energy consumption and more product amount. The performance of this new operation mode is studied through simulation of an industrial reactive batch distillation process. To simulate the transient process, a dynamic rigorous detailed model is used. Comparisons of the new operation mode with the conventional options clearly indicate the improvement by the new operation mode. However, due to the dynamic nature, initialization of such a system is a challenging problem. Thus, since the performance of the start-up procedure has a large impact on the entire batch process, we also include in the optimization problem formulation the description of the dynamic behavior of the start-up operation starting from the cold and empty batch columns as the initial state. From this issue, some useful start-up heuristics are derived.