Vapor-liquid equilibrium (VLE) in trickle-bed hydroprocessing reactors can significantly change the fluid hydrodynamics and the distribution of reacting species in both the vapor and liquid phases and, ultimately, change the reactor performance. VLE is especially important to pilot-plant studies in which ideal operating regimes (plug flow, full catalyst wetting, absence of reactor wall effects, etc.) are desired to generate reliable, reproducible, and representative data for commercial scale-up and kinetics studies. In this article, we report VLE flash experiments that were conducted in a continuous-flow unit with hydrogen and various petroleum middle distillates under typical hydrotreating conditions to study the relative distribution of the oil in the two phases. The experimental data were further used to evaluate the interaction coefficients, required to perform VLE flash calculations, between hydrogen and hydrocarbon boiling-point pseudocomponents. Furthermore, flow hydrodynamics were predicted in a pilot-plant trickle-bed reactor for hydrotreating two different middle distillate feeds to provide a mapping of operating conditions under which the desired operating regimes could be maintained.