Quantitative ultrasound techniques for characterizing red blood cell (RBC)aggregation rely on a theoretical scattering model to fit the measured backscatter coefficient (BSC). The scattering theories commonly used assume spherical shape of RBC aggregates and an isotropic structure factor. The aim of this work was to study the anisotropy of ultrasonic backscatter from blood to determine if measuring the angular dependent BSCs could improve the differentiation between healthy and pathological RBC aggregation (i.e. anisotropic rouleaux versus isotropic clumps). Experiments were conducted at a physiological hematocrit of 40% on porcine blood sheared in a Couette flow device combined with a 15-MHz focused transducer. The transducer was placed in order to obtain different insonification angles ranging from 60° to 120° with respect to the flow streamlines. The flow contains RBCs treated with dextran 500 kDa to promote aggregation. In parallel, simulations were conducted by considering a collection rouleaux-shaped scatterers uniformly randomly distributed using a Monte Carlo algorithm. Results exhibit angular dependent BSC behavior for aggregating blood in both simulations and experiments. The peak of BSC amplitude at 90° observed in experiments could be explained by rouleaux structures aligned with the streamlines. For individual RBCs re-suspended in saline solution, the experimental BSC amplitude versus insonification angle is also strongly anisotropic with a minimum value at 90°, which was not expected. This anisotropic behavior cannot be simulated by considering the Monte Carlo algorithm but are due to non-hydrodynamic forces in sheared concentrated suspensions, as reported previously in (Blanc, Journal of Rheology, 2012)for hard spheres. To conclude, the anisotropy observed in sheared blood originates from both aggregate structure (aligned or not with the flow)and the anisotropic structure factor of effective scatterer.