Multivessel batch distillation is a promising alternative to conventional batch distillation. Earlier studies proved the feasibility of temperature control in a closed operation mode, that is, when no product is removed until the end of the process. In this article, the influence of the reflux strategy during the initial start-up period is investigated in detail. This is a very important task in terms of the development of automation procedures in an industrial realization. The work is divided into three main parts. First, a rigorous dynamic model is introduced to describe the behavior of a multivessel batch distillation during start-up. Then, two experiments carried out on a laboratory scale column were chosen to validate the model. Finally, a sensitivity study is presented observing composition response while changing the reflux strategy. The results show that the process can be improved by applying a high reflux ratio and establishing the hydraulics as soon as possible.