The effect of liquid quenching during the hydroprocessing of a heavy crude oil in a fixed-bed reactor system was explored. Experiments were carried out at various operating conditions in a pilot plant equipped with two fixed-bed reactors in series loaded with a triple catalyst system and necessary hardware for injecting quench fluids between reactors. The feed and quench liquid were prepared by splitting a heavy crude oil into two fractions, called light and heavy fractions. The heavy fraction was used as the feed to the reactors, whereas the light fraction was injected between reactor s as the quenching liquid. To establish a reference case, a conventional hydrogen quenching scheme was also evaluated by injecting hydrogen instead of the light fraction. It was observed that hydrogen quenching produced only marginally better quality because of a more favorable H-2/oil profile. Yet, it was determined that this approach (hydrogen quenching) requires the handling of large volumes of gas, which increases compressor capacity and equipment size. Liquid quenching, on the other hand, decreases the reaction severity by increasing the liquid hourly space velocity (LHSV), which affects product quality although not significantly. Compared with hydrogen quenching, liquid quenching dramatically reduces the quench volumetric rate and consequently compression costs, which makes this approach an economically attractive option for industrial application.