BACKGROUND: Unlikely crystalloid, hydroxyethyl starch (HES) solution as a replacement fluid during acute normovolemic hemodilution (ANH) compromises hemodilution-mediated hypercoagulability. However a new HES [130/0.4] preparation may influence hemostasis minimally due to an improved molecular distribution in plasma. This study was designed to estimate the effect of low molecular weight HES solutions (HES [70/0.55] and HES [130/0.4]) during ANH. METHODS: Twenty healthy patients scheduled for spine surgery were randomly enrolled in HES 70 and HES 130 groups. All patients underwent moderate ANH before the induction of anesthesia. While whole blood (20 ml/kg) was being procured, blood deficits were replaced with the same volume of the respective HES solutions. Hematocrit, platelet count, plasma fibrinogen concentration, ionized calcium level, and factor VIII activity were assayed and thrombelastography (TEG) was performed before and after ANH. Statistical tests were conducted to determine the effect of each HES solution. RESULTS: Hematocrit, platelet count, plasma fibrinogen concentration and factor VIII activity were lower than baseline in each group after ANH. According to TEG findings, MA was lower in both groups but R shortened and alpha enhanced in the HES 130 group alone. Comparisons between the HES 70 and HES 130 groups showed that hematocrit, R, alpha and MA changes during ANH differed significantly between the two (repectively, P = 0.019, 0.043, 0.023 and 0.019). CONCLUSIONS: HES [130/0.4] solution administered for ANH impairs the hemostatic system to a lesser extent than HES [70/0.55] solution. However, because the volume effect of HES [130/0.4] solution persists for a few hours, a chance of hypovolemia remains during ANH.