This mainly theoretical work is devoted to the study of the contribution of the cell-free layer (CFL) near the vessel wall to hemodynamics in a large coronary artery with stenosis to assess the relevance of CFL modeling to the needs of interventional cardiology. An Euler–Euler model considering blood as a two-component fluid with a discrete phase of erythrocytes and a liquid plasma phase was applied to a simple 2d vessel with 65% stenosis. It was found that both the CFL thickness and the local contribution of the CFL thickness to hemodynamics are inhomogeneous along the vessel. The effects of CFL on the velocity profiles, vortex formation, hematocrit, viscosity, and wall shear stresses in the area of stenosis were determined. To demonstrate the significance of CFL modeling for prognostic purposes, the same hemodynamic conditions, analyzed using a one-component model, were also considered. A comparison analysis showed that the existence of CFL resulted in a significant overestimation (up to over 100%) of the main hemodynamic characteristics of the flow obtained using the model based on the Carreau equation.