Two von Willebrand factor (vWF):collagen binding (activity) assay (CBA) kit methods are commercially available. A monoclonal antibody (MAB)-based enzyme-linked immunosorbent assay (ELISA) system reported to correlate with a standard vWF:ristocetin cofactor (RCof) assay is also commercially available. It is marketed as a vWF:Activity assay and is available in 2 assay version formats. In the present study, these 4 vWF-activity options were compared directly with in-house vWF:CBA ELISAs for their ability to detect von Willebrand disease (vWD) and identify qualitative vWF defects. The 2 MAB-based systems detected vWD but could not specifically identify qualitative vWF defects, although the recently modified Mark II kit was more effective for the latter compared with the original Mark I kit. All vWF:CBA methods, including in-house and commercial, also effectively detected vWD but differed in their ability to identify qualitative vWF defects. Effectiveness was highest using the in-house reference vWF:CBA (using a type I/III collagen mix product from equine tendon), the Gradipore vWF:CBA (also uses equine tendon-derived collagen), or the in-house vWF:CBA methods using type III human collagen at a relatively low concentration (1 or 3 micrograms/mL, without covalent linkage). The IMMUNO vWF:CBA seemed to be the least effective among the vWF:CBA methods for detection of qualitative vWF defects.