An important issue concerning the use of soft contact lenses is comfort, which, among other factors, has been related to the level of friction between the anterior side of the lens and the inner eyelid. Although several studies have been carried out to investigate the frictional properties of contact lenses, these have not taken the physiological environment of the eye into account. In use, lenses are in contact with proteins present in tears, with corneal cells and with the palpebral conjunctiva (clear membrane on inner eyelid). The focus of this study was to establish a biologically relevant measurement protocol for the investigation of friction of contact lenses that would mimic the eye's physiological environment. By optimizing parameters such as the composition of the friction counter surface, the lubricant solution, the normal load and the velocity, an ideal protocol and setup for microtribological testing could be established and used to perform a comparative study of various commercially available soft contact lenses.