Studies were performed to elucidate the mechanism of alum gel coagulation upon freezing and drying and its relationship to vaccine potency loss and to develop a novel freeze-drying process for the production of stable alum-adjuvanted vaccine formulations suitable for conventional needle injection and epidermal powder immunization (EPI). The alum hydroxide-adjuvanted hepatitis-B surface antigen (Alum-HBsAg) and the alum phosphate-adjuvanted diphtheria and tetanus toxoids (Alum-DT) were dehydrated by freeze drying (FD), spray drying (SD), air drying (AD), or spray freeze drying (SFD). After drying by FD, SD, or AD, alum gels coagulated when examined by optical microscopy and particle size analysis. In addition, desorption of antigen molecules from the coagulated when examined by optical microscopy and particle size analysis. In addition, desorption of antigen molecules from the coagulated alum gel upon reconstitution appeared to be difficult, as indicated by attenuated band intensity on SDS-PAGE. In contrast, SFD alum gels turned a homogenous suspension upon reconstitution, suggesting minimal alum coagulation. In the mouse model, the in vivo immunogenicity of SFD Alum-HBsAg was preserved, whereas the FD Alum-HBsAg suffered significant immunogenicity loss. Grinding of coagulated FD Alum-HBsAg into smaller particles could partially recover the immunogenicity. In a guinea pig study using EPI, the SD Alum-DT formulation was not immunogenic, but the SFD Alum-DT formulations had a vaccine potency comparable to that of the untreated DT administered by I.M. injection. Overall, the relationship of coagulation of alum gel upon reconstitution and the loss of vaccine potency was established in this study. Alum gels became highly coagulated after dehydration by spray drying and traditional freeze-drying processes. However, freezing rate played a critical role in preserving the adjuvant effect of alum and fast freezing decreased the tendency of alum coagulation. Spraying the alum gel into liquid nitrogen represents the fastest freezing rate achievable and resulted in no discernible alum coagulation. Therefore, SFD presents a novel and effective drying process for alum-adjuvanted vaccine formulations and is particularly valuable for dry powder applications such as EPI.