Administration of fluids to maintain or restore intravascular volume is a common intervention after hemorrhagic shock, but there is uncertainty whether the choice of fluid significantly influences outcome. Systemic parameters, microvascular perfusion, and functional capillary density were used to characterize resuscitation from hemorrhagic shock with hydroxyethyl starch (HES) of different molecular weights. Studies were made in the hamster window chamber model to determine their effects on blood rheological properties, restoration of perfusion and coagulation changes. Moderate hemorrhagic shock was induced by controlled arterial bleeding of 50% of blood volume, and hypovolemia was maintained for 1 h before resuscitation. Twenty-five percent of blood volume was restituted, and recovery was followed over 60 min. Low-molecular weight (MW) HES (L-HES) 130 kd, degree of substitution (DS) 0.40, and high-MW HES (H-HES) 670 kd, DS 0.75, were used as resuscitation fluids. Microthrombi formation was induced by endothelial laser irradiation. H-HES improved systemic conditions, microcirculatory flow, and metabolic recovery after resuscitation when compared with L-HES. Mean arterial pressure was significantly improved after resuscitation with H-HES compared with L-HES, but lower than baseline and the sham group. Thrombus formation was impaired in both groups after resuscitation compared with sham. There was no difference in microthrombi formation between low- and H-HES for medium and large laser endothelial injuries. Our results indicate that fluid resuscitation with HES may increase the risk of bleeding, but not necessarily caused by the properties (MW and DS) of the colloid. Impairment of thrombus formation seems to be in part related to altered hemodynamics and transport inherent to hemodilution, leading to lowered platelet availability due to hemodilution and increased shear stress at the vessel wall when plasma viscosity is increased. The HES MW does not seem to be a factor in compromising platelet adherence on stimulated endothelium. The longer initial intravascular persistence of H-HES might result in longer-lasting volume effects.