Von Willebrand factor (vWF) abnormalities are involved in the hemostatic disturbances of uremia. Studies of vWF in both anemic and recombinant erythropoietin (EPO)-treated maintenance hemodialysis (HD) patients have given inconsistent results that could be partially dependent on the methodology. Therefore, the reciprocal relationships between four different vWF assays were studied in HD patients in relation to EPO therapy. Plasma vWF activity measured by ELISA using monoclonal antibodies against platelet glycoprotein (GP) Ibα (vWF:Act), plasma vWF antigen concentration by ELISA employing polyclonal antihuman vWF antibodies (vWF:Ag), and functional vWF activity by ristocetin-induced platelet aggregation (RIPA) in both platelet-rich plasma (PRP) and whole blood were studied in 70 HD patients. In the whole group, no correlations between these assays were found. In the non-EPO patients (n = 32), vWF:Act was correlated with vWF:Ag (r = 0.504, p = 0.003) but not with vWF activity by RIPA in PRP. In the EPO-treated patients (n = 38), vWF:Act was higher than in the untreated ones (p = 0.001), and vWF:Ag was related to the whole-blood RIPA (r = 0.386, p = 0.016). In conclusion, the platelet GP Ibα-binding epitope of the vWF molecule assessed by vWF:Act ELISA is intact in HD patients. However, this assay does not reflect the functional vWF activity as measured by RIPA in PRP. In EPO-treated patients, the GP Ibα-binding domains of vWF are more available but the plasmatic vWF monomers are neither more numerous by vWF:Ag ELISA nor more hemostatically active by RIPA PRP. The whole blood RIPA test has some potential for the quantification of vWF monomers in EPO-treated HD patients.