Hydroxyethyl starches (HES) interfere with coagulation because of their molecular structure and the amount infused during surgery. Coagulation defects include platelet dysfunction and a decrease of the VIII/von Willebrand factor complex (VIII/vWF). We examined the effects of 6% HES 200/0.6 on hemostasis by using an in vitro platelet function analyzer, the usual coagulation tests, the VIII/vWF complex assessment, and TEG analysis in patients undergoing abdominal surgery. The influence of the blood group was investigated. HES infusion induced primary hemostasis alterations, assessed by a prolonged platelet function analyzer closure time in the presence of epinephrine and adenosine diphosphate, which was not correlated with the platelet count. The decrease in VIII/vWF complex was proportional to the volume of infused HES (20 and 30 mL/kg) and was more pronounced in patients of the O blood group. The preoperative hypercoagulability status assessed by TEG analysis was reversed 24 h after HES infusion. In conclusion, 6% HES 200/0.6 induced immediate hemostasis alterations. Patients of the O blood group were likely to develop a von Willebrand-like syndrome after HES infusion. We conclude that intraoperative use of 6% HES 200/0.6 should be restricted in patients of the O blood group undergoing surgical procedures with high risk for bleeding.