Hydrocracking is a crucial refinery process that transforms heavy molecules (i.e., vacuum gas oil) into lighter and highly valued products such as naphtha, jet fuel and diesel fuel. In order to improve margins, the refiner must tackle the following points: (1) select the best catalyst stacking or combination [hydrotreatment catalyst(s) + hydrocracking catalyst(s)] and (2) optimization process: define the optimal operating conditions. The aim of this paper is to illustrate the global methodology proposed by IFPEN to answer to these points with the focus on experimental points. It is illustrated for the revamping of a fluid catalytic cracking feedstock hydrotreater (CFHDT) into a mild hydrocracker. It is divided into several steps. The first step is a virtual screening for possible catalyst stacking and operating conditions. It is based on hydrodenitrogenation (HDN), hydrodesulfurization (HDS) and hydrocracking (HDC or HCK) kinetic modeling, and product property correlations. The second step is to define the design of experiments in order to check the results provided by the kinetic models. The third step is to check the virtual stacking using pilot plant tests. This can be carried out by using a high throughput testing (HTT) experiment pilot plant (reactor volume around 0.5−1 cm 3 ). The fourth step is to test the prescreened catalyst stacking in a classical pilot plant (reactor volume around 50−200 cm 3 ) because they are more robust to refractory feedstock, and it can produce additional product volume for further analysis. The fifth step is to update the kinetic models using the new experimental points. This paper shows also that: (1) it is possible to process refractory feedstock in the HTT experiment pilot plant; (2) catalyst ranking is similar in HTT and classical pilot plants; and (3) in mild hydrocracking, performances (HDS, HDN, and HDC) are similar between HTT and classical pilot plants. However, the classical pilot plants are still useful for process study (optimize each temperature bed, estimate product properties for specific cuts, etc).