Structural characterization of new alpha/gamma-peptide foldamers containing the cyclically constrained gamma-amino acid I is described. Crystallographic and 2D NMR analysis shows that gamma residue I promotes the formation of a 12/10-helical secondary structure in alpha/gamma-peptides. This helix contains two different types of internal H-bond, and the data show that the 12-atom C=O(i) -> HN(i+3) H-bond is more favorable than the 10-atom C=O(i) -> HN(i-1) H-bond. Several foldamer helices featuring topologically distinct H-bonds have been discovered, but our findings are the first to show that such H-bonds may differ in their favorability.