This work presents the modeling and analysis of heavy oil hydroprocessing in a fixed-bed reactor system with liquid quenching. Hydroprocessing tests at various operating conditions were conducted in a multi-reactor pilot plant, with inter-bed injection of quench gas or liquid. Based on the experimental information, a heterogeneous plug-flow reactor model was developed to simulate the behavior of the process with both gas and liquid quenching. Major reactions such as hydrodesulfurization (HDS), hydrodenitrogenation (HIDN), hydrodemetallization (HDM), hydrodeasphaltenization (HDAs), and hydrocracking (HCR) are considered. The model showed to predict quite well the experimental data in the range of the studied operating conditions. The analysis was extended to simulate the commercial process and to analyze different quenching schemes from an economical point of view. It was determined that the liquid quenching scheme reduces the consumption of utilities and equipment requirements, and thereby total costs, without affecting product quality. (C) 2009 Published by Elsevier B.V.