Reactive crystallization is widely used in the manufacture of active pharmaceutical ingredients (APIs). As APIs often have low solubility, traditional stirred tank reactors and the route of process operation and control using metastable zone width are not effective. This work investigated the integration of an impinging jet mixer and a stirred tank crystallizer that can take advantage of both the reaction and crystallization characteristics, the focus being on design optimization and scale-up using process analytical techniques based on the Fourier transform infrared spectroscopy and focused beam reflectance measurement, as well as X-ray diffraction and particle imaging Morphologi G3. The parameters for process operation and design of the impinging jet mixer were optimized. The research was carried out with reference to the manufacture of an antibiotic, sodium cefuroxime, first in a 1L reactor, then a 10L reactor. The crystals produced showed higher crystallinity, narrower size distribution, higher stability, and purity. (c) 2014 American Institute of Chemical Engineers AIChE J, 61: 503-517, 2015