This research activity proposes a sensitivity analysis of the molecular distillation process by focusing the attention on the response of the overall distillate flow rate under several conditions of distillation temperature and feed flow rate. Specific equations to characterize physicochemical properties of petroleum residues have been formulated by means of ASTM-based experimental campaigns combined with specific optimization techniques. The steady state refining process simulator by Petrobras coupled with appropriate finite-difference methods is adopted for the simulation of a heated and extremely low-pressure falling film evaporator to separate a heavy residue 673.15K+ of Gamma + Sigma crude oil. Numerical results are validated on the experimental points. Crown Copyright (C) 2011 Published by Elsevier B.V. on behalf of The Institution of Chemical Engineers. All rights reserved.