Clinical observations suggest that red blood cells (RBCs) participate directly in hemostasis. We designed an in-vitro system aimed at evaluating the hemostatic function of RBCs. Blood samples were collected from 20 healthy volunteers and packed RBCs (PRBCs) were supplied by the Shaanxi Province Blood Center. We investigated the effect of RBCs and hemoglobin concentration on the hemostatic function in vitro by thromboelastography. The activation of platelets was evaluated by detecting their active markers through flow cytometry. PRBCs ameliorated the coagulation disorders induced by dilution of the blood in vitro. However, addition of hemoglobin did not increase the blood coagulation, as the level of hemoglobin was negatively correlated to the clot index. Furthermore, washing PRBCs to remove contaminating residual clotting factors and platelets excluded that the coagulation effect of the PRBCs transfusion was because of the RBCs itself. Platelet activity in PRBCs exposed to storage greater than 3 weeks was not significantly reduced consistent with it being a possible contributor. Therefore, we postulate that the suspected coagulation effects ascribed to the PRBCs at transfusion may simply be because of residual clotting factors and active platelets incompletely removed in the preparation of PRBCs rather than because of the red cell membrane or its contents.