The distribution of vanadium (V) compounds in the petroleum vacuum residuum (VR) and their transformations in hydrodemetallization (HDM) were investigated. V compounds in the VR and its hydrotreated products were extracted by different solvents in sequence to obtain methanol, dimethylformamide (DMF), and toluene extract fractions. The extracts were further separated into several subfractions using silica gel chromatography with various polar solvents. Positive-ion electrospray ionization (ESI) Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) analyses was used to characterize V compounds before and after HDM. The contents of V compounds in the methanol, DMF, and toluene extracts were 9.04, 22.19, and 62.58%, respectively. The V compounds in the methanol extract were mainly porphyrin with a molecular formula of CnHmN4V1O1, which were found undergoing side-chain cracking and could be removed through hydrotreating. CnHmN5V1O2 species were found in the DMF extracts, which can be easily converted or removed under severe reaction conditions. The V compounds in the toluene extracts were most resistant for hydrotreating, which were speculated as vanadyl porphyrins with complex substituent groups attached to the core porphyrin structures. The results indicated that a highly active HDM catalyst should possess a highly active hydrogenesis property and macropore size distribution for the different V compounds removed.