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Emulsions are usually generated in high-pressure homogenization chambers. The flow field is these units are typically highly turbulent and chaotic, and mechanisms for drop formation under these conditions are not well understood. In this paper, we have applied the PBE modeling approach to droplet break-up in a high pressure homogenizer using mechanistic functions for breakage rate. We have compared our modeling results to experimental data that we have obtained on a model oil-in-water emulsion. In principle, once these functions are known, the PBE approach can be used in a predictive manner to aid in the selection of process and product variables that will lead to the desired drop size distribution. This was verified for a number of test cases by changing product properties and homogenizing conditions. We observed that the population balance model did a reasonably good job of predicting the drop size distribution and therefore look promising. For cases where the model fails, we discuss strategies for improving predictions for these types of systems.