Background: Computational fluid dynamics tools are useful for their ability to model patient specific data relevant to the genesis and progression of atherosclerosis, but unavailable to measurement tools. The sensitivity of the physiologically relevant parameters of wall shear stress (WSS) and the oscillatory shear index (OSI) to secondary flow in the inlet velocity profiles was investigated in three realistic models of the carotid bifurcation. Method of Approach: Secondary flow profiles were generated using sufficiently long entrance lengths, to which curvature and helical pitch were added. The differences observed were contextualized with respect to effect of the uncertainty of the models’ geometry on the same parameters. Results: The effects of secondary velocities in the inlet profile on WSS and OSI break down within a few diameters of the inlet. Overall, the effect of secondary inlet flow on these models was on average more than 3.5 times smaller than the effect of geometric variability, with 13% and 48% WSS variability induced by inlet secondary flow and geometric differences, respectively. Conclusions: The degree of variation is demonstrated to be within the range of the other computational assumptions, and we conclude that given a sufficient entrance length of realistic geometry, simplification to fully developed axial (i.e., Womersley) flow may be made without penalty. Thus, given a choice between measuring three components of inlet velocity or a greater geometric extent, we recommend effort be given to more accurate and detailed geometric reconstructions, as being of primary influence on physiologically significant indicators.