Freeze-dried samples of sucrose with buffer salts, amino acids, or dextran have been analyzed with differential scanning calorimetry (DSC) to evaluate the use of DSC thermograms in predicting the physical storage stability. The glass transition temperature, T g, of the amorphous cake, crystallization, and melting of sucrose are observed with DSC. T g appeared to be an important characteristic of the physical stability of the amorphous freeze-dried cake. A storage temperature above T g results in collapse or shrinkage of the cake, which for a sucrose-based formulation, may be accompanied by crystallization of the sucrose. The T g of the amorphous sucrose is influenced by other components present in the cake. Dextran-40 raised T g, while the addition of glycine to the formulation lowered T g. The residual moisture content strongly influences T g, since water acts as a plasticizer of the system; the higher the moisture content, the lower the T g and the less physically stable the freeze-dried cake. Crystallization of amorphous sucrose is shown to be inhibited by high molecular weight components or ionic compounds. DSC analysis of freeze-dried cakes proved to be a powerful tool in formulation studies.