A new data-driven experimental design methodology, design of dynamic experiments (DoDE), is proposed as a means of developing a response surface model that can be used to effectively optimize batch crystallization processes. This data-driven approach is especially useful for complex processes for which it is difficult or impossible to develop a knowledge-driven model in a timely fashion for the optimization of an industrial process. Design of dynamic experiments [1] generalizes the formulation of time-invariant design variables from design of experiments, allowing for consideration of time-variant design variables in the experimental design. When combined with response surface modeling and an appropriate optimization algorithm, a data-driven optimization methodology is produced, which we call DoDE optimization. The method is used here to determine the optimal cooling rate profile, which integrates to give the optimum temperature profile, for a batch crystallization process. To examine the effectiveness of the DoDE optimization method, the data-driven optimum temperature profile is compared to the optimum temperature profile obtained using a model-based optimization technique for the potassium nitrate-water batch crystallization model developed by Miller and Rawlings [2]. The temperature profiles calculated using DoDE optimization yield response values within a few percent of the true model-based optimum values. A sensitivity analysis is performed on one case study to evaluate the distribution of the response variable from each method in the presence of parameter and initial seed distribution variability. It is demonstrated that there is partial overlap in the distributions when only variability in the model parameters is evaluated and there is substantial overlap when variability is included in both the model and initial seed distribution parameters. From this evidence, it can be concluded that the DoDE optimization method has the potential to be a useful data-driven optimization tool for batch crystallization processes where a first-principles model is not available or cannot be developed due to time and/or cost constraints. (C) 2012 Elsevier Ltd. All rights reserved.