The structure of nickel and molybdenum in silica-supported NiMo catalyst precursors, modified by the addition of various chelating ligands, was studied by means of X-ray, Raman, and UV-VIS spectroscopy. Thiophene hydrodesulfurization tests showed that a wide variety of ligands have a beneficial effect on the performance of the sulfided catalysts. The activity of catalysts prepared with nitrilotriacetic acid (NTA) and ethylenediamine (EN) was measured as a function of the ligand to Ni ratio in the catalyst precursors as well. EN gradually causes an improvement of the catalytic activity when the EN/Ni molar ratio increases from 0 to 4, while the best result for NTA is obtained when the NTA/Ni ratio is 1.5. UV-VIS spectra of NiMoEN impregnation solutions and dried catalysts showed that some EN is removed from the first coordination sphere of Ni during the drying procedure. Ni K-edge extended X-ray absorption fine structure (EXAFS) proved the presence of a Ni-Si shell and, thus, of Ni-SiO2 interactions in the catalyst precursors prepared without ligands. These interactions disappeared gradually with increasing amounts of the ligand. Raman spectroscopy and Mo K-edge EXAFS showed that Mo is present on the support as a mixture of MoO42- and polymolybdate clusters. Raman spectroscopy also suggested that these polymolybdate clusters interact with the support. Mo K-edge EXAFS spectra showed that EN has very little effect on Mo, whereas at NTA concentrations higher than 1 the [MoO3(NTA)](3-) complex is formed. The increase in activity obtained with EN and NTA is attributed to the elimination of Ni-SiO2 interactions and to the presence of the ligands in the Ni coordination sphere, whereas the decrease in activity observed in catalysts with NTA/Ni ratios above 2 is explained by the formation Of [MoO3(NTA)](3-).