Scaling up and validation of a trickle-bed reactor model were performed with the experimental information obtained during the hydro-treatment of vegetable oil in a pilot-scale reactor. The scale-up is carried out with a previously developed bench-scale reactor model that demonstrated good agreement with the experimental data. The differences in the characteristics of both reactor scales affected catalyst wetting efficiency, diffusion limitations inside the catalytic particle, and wall effects. These alterations were attributed mainly to the use of larger catalytic particles and higher surface velocities of the feedstock used in the pilot-scale reactor compared with the bench-scale reactor. In addition, the catalyst used in the pilot-scale reactor showed more effectiveness than that in the bench-scale reactor, thus presenting more triglyceride conversion. Simulations with the rector model also indicated that the higher feed flow rate and the large amount of catalyst used in the pilot-scale reactor generate a greater release of heat that makes it difficult to stabilize the reactor to reach steady state.