Catalytic hydrotreating (HDT) is a mature process technology practiced in the petroleum refining industries and used to treat the oil fractions from a crude oil distillation (CDU) unit for the removal of contaminants such as sulfur, nitrogen, etc. Hydrotreating of the whole crude oil before it goes to a CDU unit is a new technology and is regarded as one of the more difficult tasks that have not been reported widely in the public domain. Our recent study using a laboratory small-scale pilot plant shows significant improvement in middle distillate yields and quality of crude oil in terms of contaminants present. Recently, we also determined best kinetic parameters for several hydrotreating reactions using experimental data from the small-scale trickle-bed reactor (TBR), using parameter estimation techniques. With these parameters, we were able to develop a process model of TBR that was validated using the experimental data from the pilot plant. In this study, we scale up the pilot-scale TBR where the throughput of crude oil changes from 45 × 10–6 m3/h to 66.243 m3/h (10 000 bpd), the reactor height increases from 65 cm to 1061 cm, and the diameter changes from 2 cm to 399 cm. While isothermal conditions could be easily maintained in the small-scale TBR (an isothermal steady state model mentioned above was sufficient for the reactor), it is not the case for a large-scale reactor. Hence, a detailed model with energy balance was considered for the analysis of the large-scale reactor, and the temperature control issues are discussed. The ratio of reactor length to reactor diameter (L
R
/D
R) is chosen in such a way so that radial variation could be neglected and it was obtained using an optimization technique. All the main simultaneously occurring hydrotreating reactions are considered. These reactions are hydrodesulfurization (HDS), hydrodenitrogentaion (HDN), hydrodeasphaltenization (HDAs), and hydrodemetallization (HDM), which includes hydrodevanadization (HDV), hydrodenickelation (HDNi). In addition, the chemical reactions responsible for converting part of the crude oil to middle distillate are also considered. The gPROMS modeling software is used for modeling and simulation of the scaled-up TBR process.