Freeze-drying of mixed solutes is a preparative technique widely used in the pharmaceutical industry. The presence of an amorphous form or changes in the crystalline form can affect solid state stability. In this work, acetylsalicylic acid (AAS) was chosen as a model drug, and was mixed with mannitol, a commonly used bulking agent in formulation of tablets. Variations in the final freeze-dried crystalline forms were found after changing the ratios of the two co-solutes. Samples were analysed by powder X-ray diffractometry and differential scanning calorimetry. A major amorphous form and a minor crystalline delta-mannitol form were produced during the mannitol freeze-drying process. The crystal form of mannitol in the two-component system depended on the AAS:mannitol ratio. The AAS was mostly crystalline, regardless of the amount of mannitol present. A major delta-mannitol and a minor amorphous form were obtained when AAS was present in a high percentage (75% w/w). When AAS percentages of 50 and 25% (w/w) were present during the drying process, the mannitol was found in a highly crystalline form.