A novel liposome preparation method is described involving the freeze-drying of oil-in-water emulsions containing sucrose in the aqueous phase as a lyoprotectant and phospholipids in the oil as emulsifiers. The oil-in-water emulsions can be prepared by emulsification and then lyophilized to obtain dry products that will, upon rehydration, form unilamellar liposomes with a mean size of less than 200 nm, as proved by dynamic light scattering, atomic force micrographs, freeze-fracture electron micrographs, and small-angle X-ray scattering (SAXS). With or without combination with active loading, this method can be used successfully to encapsulate amphiphilic or lipophilic drugs into liposomes, although it cannot be applied to hydrophilic drugs. The lyophilized products are stable and can be rehydrated to form liposomes, even after a storage period of 10 months. Based on the encapsulation efficiency for hydrophilic drugs, as well as the scanning electron micrograph and SAXS of the freeze-dried products, a unique liposome formation mechanism is proposed.