Three crystal structures of donepezil salts formed with sulfonic acids were obtained. Interestingly, donepezil-besylate and donepezil-tosylate share similar crystal molecular conformations and crystal packing. On the basis of PXRD patterns, donepezil-mesylate and donepezil-esylate are likely to share similar crystal structures. The sulfonyl hydroxides of all three sulfonic acids form an intermolecular hydrogen bond with the piperidyl amine of donepezil. Solid state characterization showed that the Tg’s of all four amorphous donepezil salts are similar to each other and increase significantly compared to Tg of donepezil. Stability analysis found that the amorphous salts of donepezil formed with mesylate and esylate led to significantly improved physical stability under accelerated stability conditions, but the other donepezil-sulfonic acid salts did not. Solubility data showed that mesylate/esylate salts of donepezil significantly increase the solubility of donepezil that is not shown by other salt forms. Solubility analysis indicated that the solubility of donepezil-mesylate and donepezil-esylate is extremely high compared to that of donepezil-besylate and donepezil-tosylate. We concluded that the extremely high solubility is responsible for delaying the rate of nucleation and thus improving the physical stability of amorphous donepezil. This study highlights that the aqueous solubility of amorphous material is an important factor when considering the physical stability of amorphous material under high relative humidity.