Determination of von Willebrand factor activity is required for diagnosis and classification of von Willebrand disease. In addition, von Willebrand factor activity can be of prognostic relevance in several clinical entities including thromboembolic and cardiovascular disorders in which elevated activity correlates with a poor prognosis. The HaemosIL assay (Instrumentation Laboratory GmbH, Munich, Germany) provides a new fully automated procedure for determination of von Willebrand factor activity. This assay measures binding of the von Willebrand factor to GP Ibalpha of the platelet glycoprotein complex Ib-V-IX. In our study, we analyzed 300 samples including those of patients with hereditary von Willebrand disease. The results obtained with the HaemosIL assay were compared to von Willebrand factor activities determined by established procedures. Activities determined with HaemosIL correlated with those activities determined as ristocetin cofactor (r = 0.88, p < 0.0001), collagen-binding (r = 0.93, p < 0.0001), and GP Ib-binding (r = 0.91, p < 0.0001). The comparability of results obtained by HaemosIL and the GP Ib-binding ELISA were excellent ([HaemosIL] = 0.96 infinity activity [GP Ib-binding ELISA] + 10.7), whereas activities determined by ristocetin cofactor or collagen-binding revealed more variance. Like the other assays, the HaemosIL failed to indicate a loss of high-molecular-weight von Willebrand factor multimers. The HaemosIL assay can replace the GP Ib-binding ELISA for the determination of von Willebrand factor activity. Advantages of this assay include accuracy of results, full automation, and, thus, broad availability. Since the assay does not predict the absence of high-molecular-weight multimers, multimeric analysis remains the procedure of choice for the differentiation of functional defects.