Purpose of Study: The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen and carbon dioxide to and from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow range of parameters that determine gas exchange efficiency and blood flow resistance, such as fiber packing density, path length, and frontal area. However, these parameters also affect thrombosis. Methodology: This study investigated the effect of these parameters on clot formation using 3-D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro-rods (380 micron diameter) arranged with varying packing densities (40, 50, and 60%) and path lengths (2 and 4 cm), all of which are fiber bundle parameters in commercially available artificial lung devices. Blood was pumped through the device corresponding to three mean blood flow velocities (16, 20, and 25 cm/min), which were scaled from 4 L/min flowrates in an Adult Quadrox oxygenator. Results: Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of fiber bundle enhances deposition upstream, and consequently (3) greater path length provides more clot-free fiber surface area for gas exchange than a shorter path length. Summary: These results can be used to create less thrombogenic, more efficient artificial lung designs.Figure 1. a) The experimental flow chamber was designed to be 2 or 4 cm and with a packing density of 60%, 50% or 40% rods to simulate the flow path of blood through an artificial lung hollow fiber bundle. (b) The flow circuit involved one-way flow from a syringe pump, connected to the flow chamber and then to a waste container. A manometer measured the pressure drop across each experimental device. (c) The averaged clot volumes from the microCT scans show more clot (red) at the outlets of all devices. There was also less clot in the chambers with a longer path length device, faster flow rate, and less density.