Objectives: Impaired binding of Von Willebrand factor (VWF) to platelets and to collagen due to an acquired Von Willebrand syndrome (AVWS) has been observed in patients with left ventricular assist device (LVAD) support. AVWS seems to enhance bleeding symptoms in LVAD patients. The onset of AVWS occurs a few hours after LVAD implantation and affects platelet counts and function as well. The new HeartMate III (HM III) is a left ventricular assist device featuring several design-improvements that show promise to ameliorate the severity of AVWS in comparison to its predecessor, the Heartmate II (HM II). In this study, our aim was to analyze AVWS-parameters and platelet function in patients with HM II compared to patients with HM III support. Methods: Data sets of 31 patients under HM II support and 20 patients under HM III support were analyzed pre-surgery as well as 1, 3, 7, and 30 days post-surgery. Collagen binding capacity (VWF:CB), VWF antigen (VWF:Ag) as well as VWF:CB/VWF:Ag-ratios were determined. Presence of high molecular weight multimers of VWF was investigated. Platelet counts were monitored and platelet function was tested using light transmission aggregometry. Results: The VWF:CB/VWF:Ag ratios were significantly higher in patients with HM III than HM II at day 1, 3, and 7 after implantation. More HM III patients had intact high molecular weight multimers of VWF compared to HM II during the whole study-period (HMII: 9%; HMIII: 25%). Platelet counts and functions were comparable in both study groups. The mean duration in the Intensive Care Unit was shorter in the HM III-group than in the HM II-group (HM II: 43±52 days; HM III: 28±23 days). Conclusion: Severity of AVWS was milder in patients with HM III compared to HM II, especially during the days after surgery, when usually most hemorrhagic events occur. Loss of high molecular weight multimers 30 days after VAD-implantation was observed in a lower percentage of HMIII-patients compared to HMII-patients suggesting a long-lasting beneficial effect. Taken together, these data show that design-improvements in the new HM III compared to the HM II result in an amelioration of AVWS that could result in lower bleeding diathesis. Disclosures Geisen: Roche: Research Funding. Berchtold-Herz: Novartis: Consultancy; Thoratec: Consultancy. Zieger: CSL Behring: Research Funding; Baxalta: Research Funding; Bayer: Research Funding; German Research Foundation, Bonn, Germany [ZI 486/7-1]: Research Funding.