Linear relationships between s s pK a values in acetonitrile-water mixtures and w w pK a values in pure water have been established for five families of compounds: aliphatic carboxylic acids, aromatic carboxylic acids, phenols, amines, and pyridines. The parameters (slope and intercept) of the linear correlations have been related with acetonitrile-water composition. The proposed equations allow accurate estimation of the pK a values of any member of the studied families at any acetonitrile-water composition up to 60% of acetonitrile in volume (100% for pyridines). Conversely, the same equations can be used to estimate aqueous pK a values from chromatographic pK a values obtained from any acetonitrile-water mobile phase between the composition range studied. Estimation of pK a values have been tested with chromatographic literature data.