The impact of different start-up procedures on the behavior of two azeotropic distillation columns with multiple steady states is analyzed. Several dynamic simulation results for the two study cases are presented. Through an examination of the profile evolutions corresponding to given open-loop start-up policies (manual start-up strategies), it can be seen how the column arrives at different steady states as a function of the start-up policy. This shows that it is possible to identify a set of critical values for supervision of the start-up. Also, guidelines of general validity are given with the aim of finding the appropriate start-up policy for obtaining a desired solution. A mechanistic (qualitative) approach is presented for the interpretation of the system behavior. Some connections among the system responses and the phenomenon of multiplicity are presented. Also, a quantitative, semiempirical relationship is introduced to corroborate the qualitative explanation of the system responses. Finally, closed-loop start-up policies using a simple PI controller are analyzed, showing that the desired steady state can always be achieved in these cases.