The effect of the anti-inflammatory flufenamic acid (FFA) in dipalmitoylphosphatidylcholine (DPPC)/ dihexanoylphosphatidylcholine (DHPC) bicellar systems has been investigated. For this purpose, a combination of different techniques was used, including dynamic light scattering (DLS), freezefracture electron microscopy (FFEM), cryo-transmission electron microscopy (Cryo-TEM), X-ray scattering and differential scanning calorimetry (DSC). The incorporation of FFA induced changes in the size, morphology, thermotropic behaviour and self-assembly of the initial bicellar systems. At the three temperatures studied, different structures were formed as a consequence of the incorporation of the drug in the bicelles. At 25 C, the formation of large multilamellar sheets was observed, and at 32.5 C, the vesicle size decreased, and undulated structures and discoidal bicelles appeared. At 37 C, tubular, discoidal and spherical small structures were detected. Using this experimental approach, we have attempted to characterise these bicellar systems containing FFA, which may be very promising as new vehicles for the topical application of active principles.