A structural analysis of over 80 salts and cocrystals synthesized from equimolar amounts of carboxylic acids and N-heterocycles demonstrates that salt formation as a result of proton transfer from the acid to the base frequently (11/24; 45%) results in a lattice with an unpredictable chemical (solvate) or stoichiometric composition. However, if no proton transfer takes place and the result is a molecular cocrystal, a crystal lattice with an unexpected chemical content or stoichiometry is much less likely (3/61; 5%). These results indicate that the process of converting a neutral carboxylic acid into a carboxylate anion can have important structural consequences that make structure prediction and targeted supramolecular synthesis of salts much more difficult than of cocrystals. Consequently, cocrystals may offer new opportunities for producing a greater diversity of solid forms of drug substances that exhibit the appropriate balance of critical properties for development into a viable and effective drug product.