Rebamipide is a quinolinone derivative that has been found to increase mucin production and the number of conjunctival goblet cells. A previous phase two study has shown rebamipide 2% to be better than placebo in improving the ocular surface and reducing symptoms of dryness. In this paper, the authors report on the results of a randomised, multi-centre phase three trial comparing rebamipide 2% to sodium hyaluronate 0.1% for the treatment of dry eye syndrome. In this trial, participants with dry eye were randomised to receive a four week course of either rebamipide 2% qid or sodium hyaluronate 0.1% six times daily. Patients were examined before the commencement of the trial, at two weeks, four weeks, and finally two weeks after the end of treatment. The following outcome measures were evaluated: fluorescein corneal staining score, lissamine green conjunctival staining score, tear film breakup time, Schirmer test score, subjective symptoms (foreign body sensation, dryness, photophobia, pain, and blurred vision) scored from zero (asymptomatic) to four (very severe symptoms), and overall treatment impression scored from one (markedly improved) to seven (markedly worsened). A total of 188 patients were recruited, with 93 patients receiving rebamipide 2% and 95 receiving sodium hyaluronate 0.1%. At four weeks, rebamipide 2% had greater improvement in the fluorescein corneal staining score, lissamine green conjunctival staining score, and symptoms of foreign body sensation and eye pain. There was no significant difference in the Schirmer test score or tear film break-up time. However, more patients also commented that their symptoms had markedly improved using rebamipide 0.2% (64.5%) compared to sodium hyaluronate 0.1% (34.7%). There were no serious adverse events with using rebamipide 2%; the commonest side-effect was a bitter taste occurring in nine patients (9.7%). The efficacy and safety of rebamipide 2% as demonstrated in this trial suggests that it may become a useful additional treatment option for dry eye syndrome. What is required now is a trial evaluating the longer term efficacy and side-effects of rebamipide 2% treatment.