A four objective optimization framework for preferential crystallization Of D-L threonine solution is presented. The objectives are maximization of average crystal size and productivity, and minimization of batch time and the coefficient of variation at the desired purity while respecting design and operating constraints. The cooling rate, enantiomeric excess of the preferred enantiomer, and the mass of seeds are used as the decision variables. The optimization problem is solved by using adaptation of the nondominated sorting genetic algorithm. The results obtained clearly distinguish different regimes of interest during preferential crystallization. The multi-objective analysis presented in this study is generic and gives a simplified picture in terms of three zones of operations obtained because of relative importance of nucleation and growth. Such analysis is of great importance in providing better insight for design and decision making, and improving the performance of the preferential crystallization that is considered as a promising future alternative to chromatographic separation of enantiomers. (c) 2009 American Institute of Chemical Engineers AIChEJ, 55: 383-395, 2009