The apparent second-stage dissociation constants of 3-(N-morpholino)propanesulfonic acid, 3-[(1,1dimethyl-2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid, and N-(2-hydroxyethyl)piperazine-N′-(2-hydroxypropanesulfonic acid) were determined at (25.0 ( 0.1) °C and I ) 0.1 mol dm -3 (KNO 3 ) by potentiometric pH titration in pure water and different hydroorganic solvent media. The organic solvents used were methanol, ethanol as amphiprotic hydrogen bond acceptor-donor (HBA-D) solvents, N,Ndimethylformamide, dimethyl sulfoxide, acetone, dioxane as hydrogen bond acceptor solvents, and acetonitrile as (HBA-HBD) solvent. The ESAB2M computer program was used to refine the initial estimates of the apparent second-stage dissociation constants of the three zwitterionic buffers studied. pK a2 * values change with increasing organic content of the solvent mixture. The results obtained are discussed in terms of average macroscopic properties of the mixed solvents. The implications of the results with regard to specific solute-solvent interactions, particularly stabilization of zwitterionic species, are discussed. The effects of coorganic solvents on the acid dissociation equilibria have been interpreted using solvatochromic quantitative values of Kamlet-Taft hydrogen bond acidity and basicity (R, β) and dipolarity-polarizability π * of the solvent.