Interferences from co-ions, i.e., ions with a charge sign opposite to that of the measured ion, limit the upper detection limit of ion-selective electrodes (ISEs) based on electrically neutral or charged ionophores. A theoretical description based on phase boundary equilibria is used here to predict the co-ion interference (Donnan failure) of both types of ISEs quantitatively and to compare the extent of co-ion interference in these two cases. It is shown that, for practically relevant ionophore - site ratios, Donnan failure for ISEs based on electrically charged and neutral ionophore occurs at very similar co-ion concentrations if the charged and the neutral ionophores form complexes of equal stabilities and stoichiometries. With the exception of the selective complexation of the primary ion and charged ionophores, association of two or more ions such as between ionic sites and complexes has only a limited effect on co-ion interference. If relevant at all, ion pairing is predicted to affect upper detection limits more unfavorably in the case of neutral than in the case of charged ionophore-based ISEs. Experimental determination of co-ion interference for ISEs with five different charged and two electrically neutral H+ ionophores shows that co-ion interference increases as the stability of the H+ complexes increases and confirms that co-ion interferences for charged and neutral ionophore-based ISEs indeed occur to an equal extent if their H+ complexes have the same stabilities. These results corroborate the high potentiality of charged ionophore-based ISEs.