Hexitol nucleic acids (HNA) are oligonucleotides built up from natural nucleobases and a phosphorylated 1,5-anhydrohexitol backbone. Molecular associations between HNA and RNA are more stable than between HNA and DNA and between natural nucleic acids (dsDNA, dsRNA, DNA/RNA). H-1 NMR analysis of a HNA dimer confirms the axial orientation of the base moiety with respect to the hexitol ring, and this was used as starting conformation for a molecular dynamics study of HNA/RNA and HNA/DNA duplexes. Both complexes show an A-type geometry and very similar hydrogen bonding patterns between base pairs. The relative stability of HNA/RNA versus HNA/DNA might be explained by a difference in minor groove solvatation.