The principal objective of this study is to advance the state of the art in batch distillation synthesis by providing insights into the behavior of various column configurations, including emerging column designs, using systematic parametric performance indices. Three competing column configurations—the rectifier, the stripper, and the middle vessel column—were compared in terms of various performance indices. Performance indices used include product purity and yield, design feasibility and flexibility, and thermodynamic efficiency. Product purity is related to profitability when yield is constant. Feasibility indices based on the number of plates and the reflux ratio show whether or not such a high-purity configuration is flexible for changing design and operating conditions. Thermodynamic efficiency provides a measure of effectiveness of heat exchange around the specific column configuration. Trade-offs between these performance indices are presented.