Hydrotalcites are used in technology as catalysts and anion exchangers and are important sinks for environmental contaminants. Their compositional variability makes it important, but difficult, to estimate their aqueous solubility. We report calorimetric measurements of the heats of formation of cobalt-aluminum hydrotalcite phases. The heat and free energy of formation from the elements are equal to those of mechanical mixtures of binary compounds, namely hydroxides and carbonates. The interlayer anion is much more important than the cation in determining the solubility of the hydrotalcite phase and its ability to contain or release heavy metals to the environment. Because hydrotalcites do not have an unreactive polymer as a structural core, their aqueous stability will change dramatically with composition, particularly with anion content. This simple mechanical mixture model allows prediction of aqueous solubilities and trace metal retention in a variety of geochemical settings.