Liposomes were prepared utilizing a modified supercritical process. In this method, phospholipid suspension in water was equilibrated with high pressure CO2 and the CO2-expanded liquid phase was depressurized via two protocols. In protocol (I), depressurization rate was kept constant while in protocol (II), both the depressurization rate and the pressure inside the vessel were constant. Pressure, depressurization rate and temperature were the processing parameters evaluated in terms of their effect on the properties of the liposomes obtained. Particle size of liposomes prepared by the modified supercritical method was as small as 265 +/- 4nm and 214 +/- 3 nm for protocols (I) and (II), respectively. Elevated pressure contributed to a smaller size while higher depressurization rates resulted in enhanced uniformity. Amount of unhydrated CO2 dissolved in the phospholipid bilayer seems to be important for a small particle size while release rate from between the bilayers may affect size distribution. Liposomes prepared by the modified supercritical method were stable for up to 8 and 6 weeks for protocols (I) and (II), respectively, with a high zeta potential. Protocol (II) yielded smaller and more uniform particles while protocol (I) gave higher storage stability. The modified supercritical method is more effective in liposome preparation than conventional thin film hydration method for a reduced size and enhanced stability. (C) 2015 Elsevier B.V. All rights reserved.