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Distillation columns are important separation equipment that comprise most of the investment needed in a petroleum refining plant. Utilities and energy demands, though, are a concerning factor in the current economic and environmental scenario. The present work proposes a methodology to optimize the energy consumption of a crude oil distillation column using the Distop Calibration technique that allows faster convergence than the Tray-to-Tray method. The methodology presented involves process simulation, sensitivity analysis, factorial design, and the use of response surface methodology. Results show that it is possible to achieve significant gains by changing feed temperature and rectifying vapor flow, causing a relevant reduction in energy consumption. Hence, the methodology can be used as an optimization tool to increase energetic efficiency.