Trimethoprim (TMP) is an active pharmaceutical ingredient with poor aqueous solubility. Here, we describe the cocrystallization of TMP with five co-formers, three bipyridines and two monopyridines. Cocrystallization of TMP with the bipyridines yields neutral cocrystals, and while both components are present in the lattice, they do not interact with each other via any strong intermolecular forces. Conversely, cocrystallization of TMP with the monopyridines yields salts, and included water or solvent molecules that play a key role in supramolecular assembly. Moreover, the salts exhibit significantly higher aqueous solubility than that of TMP. Two solids feature a compound on the Generally Recognized as Safe list, making them promising as ionic pharmaceutical cocrystals.