Detailed mathematical models and dynamic simulators allow describing the behaviour of single process units as well as industrial plants. In this context, it is possible to deepen the process understanding when the plant operates at nominal steady-state
conditions and even simulate unusual and unexpected scenarios that may occur during process operation. The twofold aim of this manuscript concerns (i) the operator training and (ii) the improvement of the start-up procedure to manage either unsteady or
emergency situations, without waiting for them to happen. In this sense, the safety approach is fast changing from reacting to predicting. The paper investigates in detail which sequential and/or simultaneous operations are useful for the start-up of a separation unit while controlling and improving both safety and reliability. A generalized framework is discussed according to an appropriate sequence of both control room and field operator actions. The start-up procedure refers to the dynamic simulation of a depropanizer.