The properties of starch derivatives which may be used as plasma substitutes, are dependent upon the molecular structure. Seven acetyl starch (AS) samples were determined and compared with results from hydroxyethyl starch (HES) samples. The molar masses and their distributions were determined with the combination of size exclusion chromatography and light scattering. Slightly asymmetric distributions were determined with a polydispersity Mw/Mn = 2.4 and weight-average molar masses of Mw = 250,000–300,000 g/mol for six AS samples and Mw/Mn = 3.6 and a weight-average molar mass of 766,000 g/mol for one AS sample. The average degrees of substitution (DS) and the substitution pattern were determined by high resolution NMR spectroscopy. The AS samples investigated had a DS of 0.42 to 0.81, comparable to HES, but the regioselective substitution pattern revealed differences. While for HES the position C-2 is preferred and the position C-3 has nearly no substituent, for AS both positions, C-2 and C-3, are substituted likewise. Degradability by α-amylase was tested in the laboratory for AS as well as for HES having nearly the same degree of substitution and molar mass, but C-2/C-6 = 2 for AS and C-2/C-6 = 1.4 for HES. An exponential decrease in the molar mass was observed over time, down to a limiting molar mass Mw = 50,000 g/mol for AS and Mw = 30,000 g/mol for HES, the degradation of AS occurred more slowly.