Hydroxyl groups in dextrans have been selectively oxidized to aldehyde groups by sodium periodate in a controlled fashion with a percentage of conversion ranging from 6 to 100%. Dextrans ( 10, 70, 148, 500, and 2000 kDa) and oxidized 10k dextrans have been successfully grafted to functionalized silicon surfaces. The effect of molecular weight on protein adsorption is not nearly as striking as that of the extent of oxidation. When similar to 25% of the hydroxyl groups have been converted to aldehyde groups, there is negligible protein adsorption on surfaces containing the oxidized polysaccharides. Conformations of grafted polymers depend strongly on their chemical structures, that is, the relative amounts of -OH and -CHO groups. The dependence of the chain conformation as well as the protein resistance on the balance of the hydrogen bond donors (-OH) and the acceptors (-OH and -CHO) implies the importance of chemical structure of surface molecules, specifically the interactions between surface and surrounding water molecules on protein adsorption. Oxidized dextrans are potential poly( ethylene glycol) alternatives for nonfouling applications.