Zein nanoparticles (NPs) were generated using continuous microfluidic antisolvent precipitation. Concentrations of ethanol and zein, flow ratio between continuous and dispersed phases, total flow rate, and chip configuration were examined for their effect on NP diameter and polydispersity index (PDI). These conditions were simulated using COMSOL Multiphysics and the diameter and PDI of NPs were correlated with physical parameters calculated by the software. Increasing zein and ethanol concentration increased NP diameter overall (p < 0.01 and 0.001, respectively). Increasing flow of continuous phase relative to dispersed phase decreased NP diameter and increased PDI overall (p < 0.001 for both). Increasing the total flow rate also decreased diameter and increased PDI overall (p < 0.001 for both). COMSOL results demonstrated that average pressure over the 3D interface representing 50% (v/v) ethanol is consistently inversely related with NP diameter and directly related to PDI (r = 0.9391 and 0.7491, respectively). (C) 2017 Elsevier Ltd. All rights reserved.