This work deals with the development of experimental campaign to accomplish the upgrading of a high-boiling-point petroleum fraction (atmospheric residue ATR-W 673.15 K+ with API gravity equals 11.9 and molar mass equals 2956 kg.kmol(-1)) by centrifugal reactive molecular distillation (CRMD). In this process, 30 fractions (15 distillates and 15 residues) were obtained under different operating conditions. HT-SimDis GC played an important role to evaluate the conversion degree. Furthermore, physicochemical properties and colloidal characterization were determined by ASTM standard methods and size exclusion chromatography (SEC) with UV-absorption detection, respectively. The pilot scale experiments by the CRMD process showed that it successfully upgraded the feedstock into two process streams named as distillate and residue streams using 3 and 5 wt % of zeolite-based catalyst at 483.15 K and pressure system below 50.0 Pa. Under these conditions, in the distillate streams the conversion of ATR-W 673.15 K+ was found considerably higher (65.6% at 3 wt % of catalyst and 64.3% at 5 wt % of catalyst) than that of residue stream (49.6% at 3 wt % of catalyst and 53.1% at 5 wt % of catalyst). Moreover, it was found that distillate streams exhibited values of API gravity between 19 and 21 and molar mass up 200 kg.kmol(-1). To analyze residue streams values of API gravity were approximately equal to 11.9 and molar mass between 2570 kg.kmol(-1) and 2908 kg.kmol(-1). In this respect, the CRMD process was successfully applied in order to upgrade a high-boiling-point petroleum fraction into lower boiling point products (corresponding to the distillate and residue streams).