The challenges of insufficient residence time for crystal growing and transfer line blockage in conventional continuous mixed-suspension mixed-product removal (MSMPR) operations are still not well addressed. Periodic flow crystallization is a novel method whereby controlled periodic disruptions are applied to the inlet and outlet flows of an MSMPR crystallizer to increase its residence time. A dynamic model of residence time distribution in an MSMPR crystallizer was first developed to demonstrate the periodic flow operation. Besides, process models of periodic flow crystallizations were developed with an aim to provide a better understanding and improve the performance of the periodic flow operation, wherein the crystallization mechanisms and kinetics of the glycine-water system were estimated from batch cooling crystallization experiments. Experiments of periodic flow crystallizations were also conducted in single-/three-stage MSMPR crystallizers to validate the process models and demonstrate the advantages of using periodic flow operation in MSMPR stages. (C) 2016 American Institute of Chemical Engineers AIChE J, 63: 1313-1327, 2017