A hybrid computational model was developed to interpret the formation of curcumin particles via liquid antisolvent precipitation (LASP) in three microchannel reactors (MCRs) with different confluence angles. The computational fluid dynamics (CFD) model was numerically combined with a discretized population balance approach. The nucleation kinetics were computed using an expression obtained from the nucleation rate and supersaturation equation from previous experimental data. A quantitative comparison of the particle size distributions (PSDs) demonstrated that the particles with the smallest diameters are observed right after the intersection of the three streams. Besides, the large confluence angle of 135° in the MCR presented higher population density as a result of the smaller size of the precipitated curcumin particles. These findings illustrate the efficient applicability of the hybrid model.