Model hydrodesulfurization (HDS) catalysts (Ni2.75W21, Co2.75Mo11, Ni2.75Mo11 and Ni0.9Co1.85Mo11 wt% / γ-Al2O3) were used in the HDS of dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-DMDBT), with and without addition of H2S or NH3. The NiCoMo catalyst exhibited the highest HDS performance with the additives, while NiMo was the best catalyst without the additives. A comparison of the HDS reaction mechanism via hydrogenation (HYD) and the direct desulfurization (DDS) rate constants among these catalysts showed that the ranking of HYD and DDS rate constants depended on the catalyst and the additives. The behavior of NiW was very similar to NiMo. The total rate constants (HYD + DDS) of NiCoMo were the sums of higher HYD and DDS between the NiMo and CoMo. These results showed that the NiCoMo had two kinds of active sites, similar to NiMo and CoMo. Quantum chemical studies were applied to study the inhibitions of the additives on NiW, CoMo and NiMo metal edge surfaces. The active site structure of NiW was similar to that of NiMo. The ranking of the adsorption energies of the additives on each surface was in good agreement with experiments. The ideas derived from these model feed reactions in combination with quantum chemical studies contributed to the development of novel improved catalysts which played an integral part in our new HDS process.