The solubility of gypsum in different salt solutions containing Ca, Mg, Na, Cl, and SO4was determined experimentally at 298° K. Sixteen subprograms were developed by using five methods of calculating the single ion activity coefficient and four combinations of ion pairs. Statistical analysis of the difference between the experimentally determined solubility of gypsum (average of seven data sets) and the solubilities predicted with the sixteen subprograms was used to determine the subprogram that best predicts the experimental data.Results showed that acceptable predicted values within the experimental error of measurement can be obtained by considering only CaSO4and MgSO4ion pairs. The values for the dissociation constant at 298° K for CaSO4and MgSO4ion pairs of the best subprogram were 4.9 * 10−3and 5.9 * 10−3.5, respectively. The best agreement between experimental and predicted solubility was found when a constant “1.3” was used instead of the value of the effective diameter of the hydrated ions “αi” multiplied by the coefficient “β” which involves universal constants, dielectric constant, and temperature in the Debye-Huckel theory for calculating the single ion activity coefficient.