Hydroprocessing of vacuum residue is a difficult process in which highly contaminated vacuum residue is converted into a lighter middle distillate fraction. The high boiling point vacuum residue contains many heteroatoms such as nitrogen, sulfur, and metals (Ni, V) present in porphyrin rings. These will affect the activity of the slurry phase hydrocracking catalysts. Therefore, in this study, the effect of feedstock properties on the slurry phase hydrocracking catalyst was investigated. The catalytic activities were compared with the thermal activities for all feedstock studied. It was observed that the catalytic HDM activity of a slurry catalyst was higher than that from a thermal reaction, irrespective of the feed used. The maximum catalytic conversion was obtained with the feed (MGL-VR) that contained a high amount of Ni metal. A smaller amount of hydrogen was produced with catalytic tests, confirming that hydrogenation occurs in the presence of a catalyst. Also, the higher production of lighter hydrocarbons such as methane and ethane in the catalytic process was observed. The catalytic reaction with the feed having the highest amount of asphaltene (ESR-VR) generated more than 22% of methane. This occurs because of the severe cracking of side chains of the large polyaromatic compounds. The two conversion factors were obtained at thermal (TRC) and catalytic (CRC) conditions. A correlation between the difference of residue conversion (DCn) and feedstock properties has been evaluated. The results suggest that besides the amount of asphaltene in the feed, the amount of boiling fraction above 550 °C is an important parameter to be considered during slurry phase residue upgradation. It was found that the microcarbon residue (MCR) property of the feedstock can help to predict the residue conversions. The hardness properties of the coke samples evaluated using thermogravimetric analysis (TGA) showed that in catalytic reactions relatively soft coke is produced compared with that produced in thermal reactions.