A major concern of hydroprocessing operations is that the substantial heat release produces a sharp temperature rise along the reactor, especially under start-of-run (SOR) conditions with fresh catalyst, which may induce local overheating if reaction temperature is not properly controlled by a quenching system. In this context, it is of extreme relevance to understand reactor dynamics in order to establish an optimal start-up strategy. This work presents an analysis of the transient behavior of a front-end fixed-bed hydrodemetallization (HDM) process based on a three-phase dynamic reactor model. The mathematical model was constructed and fitted on the basis of bench-scale experiments. The model accounts for major hydroprocessing reactions, mass-transfer and catalyst deactivation. The model was applied to analyze industrial reactor performance subjected to process parameter variations. The simulations revealed that quenching must start before or as soon as the hydrocarbon front reaches the quench box in order to avoid overheating and that under SOR conditions special care must be taken into account to select the lowest possible feed temperature. It was determined that the safest start-up strategy was to stabilize the catalyst at low temperature followed by a soft temperature increase in order to meet product specifications in a short period of time. (C) 2012 Elsevier B.V. All rights reserved.