This work presents a process design methodology that evaluates the distillation systems based on exergetic, economic, and greenhouse gas (GHG) emission aspects. The aim of the methodology is to determine how these three features should be applied in process design to obtain information about the accuracy of the design alternatives. The methodology is tested and demonstrated on three different energy-integrated distillation systems: the direct sequence with backward heat-integration (DQB), fully thermally coupled distillation column (FTCDC), and sloppy distillation system with forward heat-integration (SQF). The average relative emission saving is the highest for the DQB scheme and this sequence shows the most flexible range of use. The case studies prove the accuracy of our evaluation methodology. On the other hand, it highlights and demonstrate.s that the exergy analysis can predict the results of the economic study and the environmental evaluation to make the decisions, associated with process design, much simpler. (C) 2009 American Institute of Chemical Engineers AIChE J. 56: 1776-1786,2010