Introduction: Measuring in vivo blood flow and Wall Shear Stress (WSS) in particular is still limited by current imaging technology and is generally overcome using Computational Fluid Dynamics (CFD). Pre-processing and mesh generation required to discretize the fluid domain are time-consuming, operator-dependent, and the quality of the resulting mesh is often suboptimal, especially for WSS calculations. Methods: A biplane angiogram of a left coronary artery was acquired using the Allura 3D-CA (Philips Medical System) and exported into the open-source pyFormex (http://www.pyformex.org) to generate a structured and conformal hexahedral computational mesh [1]. Starting from the same coronary tree, seven hexahedral meshes (HEX series) were generated with the new procedure as well as nine tetrahedral meshes with prismatic boundary layer (TET series) for comparison using Gambit and TGrid. All the meshes of the HEX and the TET series (50,000 to 3,200,000 cells) have been used for steady state CFD calculations under identical conditions (Fluent). WSS has been reported to be a critical parameter in grid-independence analysis and therefore has been chosen as quantity to use for comparison [2]. Results: Area-weighted-WSS values on two bifurcations (indicated in Fig. 1) show that the HEX series converges faster than the TET series (Fig. 2 top panel). Stronger difference has been found on the local hemodynamics, evaluated by measuring the WSS along a line as indicated in Fig. 1. The WSS predicted with TET meshes up to 1,000,000 cells is quantitatively but also qualitatively wrong (Fig. 2, bottom left panel). The minimum number of cells needed to reach grid–independent WSS values (percentage difference relative to the finest mesh < 5 %) were 300,000 and 2,000,000 for the HEX and the TET series respectively, requiring 14-fold longer CPU time for the TET series on the same computing infrastructure [1]. Conclusions: HEX and TET meshes perform differently in reaching mesh-independent values of WSS (mesh-independent value is a necessary, not sufficient, condition for the correctness of CFD results): HEX meshes predict the final WSS pattern and approximate the final values of WSS even with low number of cells, while TET meshes may provide misleading results in complex flow areas not only quantitatively (e.g. peak value of the WSS) but also qualitatively (e.g. spatial location of the peak value) when not converged, and require much longer computational time. Such effects are related to high numerical diffusion associated to unstructured meshes and are likely to be amplified in case of pulsatile flow simulations. The novel meshing framework is also applicable to triangulated surface models (e.g. STL) [3]. References [1] De Santis G et al., 2010, Med Biol Eng Comput, in press. [2] Prakash S, Ethier CR, 2001, J Biomech Eng 123:134. [3] De Santis G et al., CMBBE, submitted.