von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder and can also arise as an acquired syndrome (AVWS). These disorders develop due to defects and/or deficiency of the plasma protein von Willebrand factor (VWF). Laboratory testing for these VWF-related disorders requires assessment of both VWF level and VWF activity, the latter requiring multiple assays because of the many functions carried out by VWF to help prevent bleeding. The current paper describes several protocols for assessment of VWF activity by means of VWF ristocetin cofactor (VWF:RCo). These assays identify VWF activity by quantitative assessment of VWF protein adhesion to platelets or other particles and subsequent detection of the adhered VWF as facilitated by inclusion of ristocetin. The most commonly performed assays for VWF:RCo comprise platelet agglutination assays, latex agglutination assays, and chemiluminescent assay (CLIA), with three of these described in this chapter.