Acquired von Willebrand Syndrome (AvWS) is known as a frequent bleeding complication in patients on ventricular assist device (VAD) support. Clinicians demand that the requirements for VADs with regard to hemocompatibility should also include low susceptibility for AvWS. Clinical AvWS diagnosis is known to be a complex, high-price, and time-consuming analysis. This article investigates an easy-to-handle, time-efficient, and inexpensive method for comparative AvWS investigations in vitro. Von Willebrand Factor activity level (vWF:Ac) and von Willebrand Factor antigen level (vWF:Ag) were chosen from the complete set of clinically established parameters. Blood plasma (human and porcine) was exposed to an inhomogeneous shear field in a shear-inducing test set up for up to 4 h. Plasma samples were drawn after different load periods and analyzed for vWF:Ac and vWF:Ag. vWF multimer analysis of selected samples were used as reference for determination of high molecular weight multimer (HMWM) loss. AvWS was detected after 20 min of shear load via vWF:Ac/vWF:Ag ratio and multimer analysis. A good correlation between the vWF:Ac/vWF:Ag ratio and HMWM loss (multimer analysis) was found for human plasma. AvWS characteristics of human and porcine plasma for analyzed samples were comparable. A correlation between vWF:Ac/vWF:Ag ratio and HMWM in porcine plasma could not be found. Results gained in this study indicate that vWF:Ac/vWF:Ag ratio is sensitive enough for comparative AvWS investigations in vitro with human blood. The applicability of the method suggested in this article for AvWS characterization in porcine blood needs to be investigated in further studies. The selection of analysis kits promises a less cost- and labor-intensive, time-consuming, and complex method for comparative AvWS investigations in vitro compared with AvWS diagnosis in patients.