Precipitation of BaSO4 nanoparticles was studied for the first time in a specially designed rotating packed bed (RPB), which allowed sampling at different radial positions to provide better insight of the mechanism of precipitation in RPB. Particle size and morphology were characterized by TEM, while the quality of synthesized BaSO4 powders was analyzed by XRD and BET, and compared with those prepared in a stirred-tank reactor. The important role of the inlet region of the RPB in the whole precipitation process was experimentally confirmed, as a significant essence for the design of industrial RPB for the precipitation of sparingly soluble materials. The effects of different operating conditions on particle size were also investigated, showing that particle size decreases with increasing rotational speed and liquid flow rate, due to the enhancement of micromixing in the RPB.