Wet granulation in twin-screw extrusion machinery is an attractive technology for the continuous processing of pharmaceuticals. The performance of this machinery is integrally tied to its screw design yet little fundamental knowledge exists in this emerging field for granulation to intelligently create, troubleshoot, and scale-up such processes. This study endeavored to systematically examine the influence of different commercially available screw elements on the flow behavior and granulation mechanics of lactose monohydrate saturated at low concentration (5-12%, w/w) with an aqueous polyvinyl-pyrrolidone binder. The results of the work showed that current screw elements could be successfully incorporated into designs for wet granulation, to tailor the particle size as well as particle shape of an agglomerate product. Conveying elements for cohesive granular flows were shown to perform similar to their use in polymer processing, as effective transport units with low specific mechanical energy input. The conveying zones provided little significant change to the particle size or shape, though the degree of channel fill in these sections had a significant influence on the more energy-intensive mixing elements studied. The standard mixing elements for this machine, kneading blocks and comb mixers, were found to be effective for generating coarser particles, though their mechanisms of granulation differed significantly.