Ab initio calculations at the Hartree-Fock 6-31G and 6-31G* levels are used to determine the effect of additional hydrogen-bonding groups on the strength of the N-methylacetamide dimer hydrogen bond. Results are given for one, two, or three hydrogen bonds involving water, ethanol, ethylene glycol, and trifluoroethanol. The cooperative effect due to multiple hydrogen bonds can be as large as 5.8 kcal/mol; the magnitude of the effect depends on the nature and the number of ligands. Ethylene glycol and trifluoroethanol are found to lead to larger stabilization than does water, which is of interest in view of experimental observations of the effect of these solvents on peptides and proteins. The observed cooperativity also has implications for the stability of helices, multiply stranded beta pleated sheets, and supramolecular structures involving hydrogen bonds.