HES are high-polymeric glucose compounds obtained via hydrolysis and subsequent hydroxyethylation from the highly-branched amylopectin contained in maize. Initially, the HES were only characterized by their in vitro molecular weight (Mw), without consideration of the in vivo hydrolysis by alpha-amylase. The degree of substitution and the molar substitution ratio quantify the hydroxyethylation. The glucose units can be substituted at carbon 2, 3 and 6 leading to various substitution patterns. This pattern is described with the C2/C6 hydroxyethylation ratio. The higher the degree of substitution and the C2/C6 ratio, the less the starch is metabolized. The in vitro Mw, the degree of substitution and the C2/C6 ratio are the main determinants of the in vivo Mw which is clinically relevant. Haemorrhagic complications that occur after infusing larger volumes of HES can be avoided with a starch of low in vivo Mw. This is not only due to a lesser effect on the coagulation system which prevents an acquired type I von Willebrand syndrome, but also to a smaller decrease in platelet volume, since platelet volume and platelet function are positively correlated. In addition, HES with low in vivo Mw has significantly better rheological effects than HES with a high in vivo Mw, as high Mw macromolecules affect plasma viscosity negatively. Furthermore high Mw HES macromolecules lead to a distinctive decrease in fibronectin concentration that reflects saturation of the reticuloendothelial system. Another advantage of low in vivo Mw HES is its rather short half-life. Patients with an increased bleeding risk, microcirculatory disturbance or affected RES should receive HES with low in vivo Mw. In the future, HES should be mainly characterized by the in vivo and not the in vitro Mw.