2- O-Sulfo-α- l-iduronic acid (IdoA2S) is one of the main components of heparin, an anticoagulant and antithrombotic polysaccharide able to potentiate the inhibitory effect of antithrombin over plasma serine proteases. This monosaccharide unit adopts an equilibrium between chair ( 1 C 4) and skew-boat ( 2 S O) forms as a function of heparin sequence size and composition. Although the prevalence of the 1 C 4 chair conformation in monosaccharides is understood, the reasons for the increase in 2 S O contribution in the whole polysaccharide chain are still uncertain. In this context, 0.2 μs molecular dynamics simulations of IdoA2S-containing oligosaccharides indicated that stabilization due to intramolecular hydrogen bonds around IdoA2S is highly correlated ( p ⩽ 0.001) with the expected conformational equilibrium for this residue in solution. This behavior explains the known effect of different heparin compositions, at the monosaccharide level, on IdoA2S conformation in biological solutions.