SummaryFive expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; X3), Biostate® (X3) and Humate/Haemate (X3). All laboratories blind tested for FVIII:C, VWF:Ag and VWF:CB, four tested for VWF:RCo, and one performed VWF:Multimers. The study yielded inter-laboratory CVs for VWF:Ag and FVIII:C around 10–15%, and for VWF:CB and VWF:RCo around 20%, significantly lower than those of previous multi-laboratory surveys. All three lots of AHF HP contained in the vicinity of 25 U/ml FVIII:C, around 60–75 U/ml of VWF:Ag, but only 30–45 U/ml of VWF:CB and 40–50 U/ml of VWF:RCo (thus, CB/Ag ratio around 0.5–0.6 and RCo/Ag ratio around 0.6–0.7). Study determined that FVIII:C and VWF:RCo levels were similar to manufacturer assigned levels. Some loss of the high molecular weight (HMW) multimers was observed, together with an intense low molecular weight (LMW) VWF band consistent with some reduction or proteolysis of HMW VWF. All three lots of Humate/Haemate contained in the vicinity of 23–32 U/ml of FVIII:C, 70–105 U/ml of VWF:Ag, 50–90 U/ml of VWF:CB and VWF:RCo (i. e. CB/Ag ratio around 0.6–0.9 and RCo/Ag ratio around 0.6–1.1). Study-determined FVIII:C and VWF:RCo levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was also observed with Humate/Haemate. All three lots of Biostate contained in the vicinity of 40–55 U/ml of FVIII:C, 105–170 U/ml of VWF:Ag, 90–150 U/ml of VWF:CB, and 90–135 U/ml of VWF:RCo (i. e. CB/Ag and RCo/Ag ratios around 0.7–1.0). Study-determined FVIII:C levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was not observed with Biostate. The defined pattern of increasing CB/ Ag from AHF HP to Humate/Haemate and Biostate was consistently observed in study data from each of the five laboratories. In conclusion, study findings indicate some differences in the retention of functional/ HMW VWF between factor concentrates, and this is expected to have significant implications in terms of clinical efficacy for therapy in VWD.