Background A number of new assays with different measuring principles are available to measure von Willebrand factor (VWF) glycoprotein Ib (GPIb)‐binding activity, but little is known about how these assays might behave differently for subtypes of von Willebrand disease (VWD). Objectives The Comparison of Assays to Measure VWF Activity (COMPASS‐VWF) study was designed to compare all available VWF GPIb‐binding activity assays for VWF. We specifically searched for particular assay behavior differences. Patients/Methods To sort out random differences from systematic assay behavior deviations, all assays were performed in different laboratories on the same samples in a blinded fashion. Samples from 53 normal controls and 42 well‐characterized VWD patients were reanalyzed in this study to dissect assay‐specific discrepancies. Results No assay behavior differences were found for 53 normal controls. For VWD patients, we found the following systematic assay behavior patterns: (a) All ELISA assays for VWF:GPIbR as well as VWF:GPIbM are insensitive to detect the low VWF activity of VWD type 2B patients with loss of high molecular weight multimers; (b) VWF:Ab assay reports higher activity for the p.V1665E mutation than all other assays; and (c) all ristocetin‐based assays (including VWF:RCo using fixed platelets) but the AcuStar assay report discrepantly low VWF activity for the p.P1467S polymorphism. No systematic assay‐specific difference was observed for either the particle agglutination VWF:GPIbM assay or the AcuStar assay using magnetic beads. Conclusions Different assay principles may lead to discrepant results for certain VWD types or mutations. Therefore, a more extensive study for a large number of patients is needed to better characterize the incidence and relevance of such assay‐specific differences.