OBJECTIVE: The aim of this study was to compare the cost-effectiveness of emedastine, a new topical anti-histaminic, with topical levocabastine in Belgium, France, Germany, Netherlands, Norway, Portugal and Sweden, in the treatment of allergic conjunctivitis. METHODS: A randomized, controlled, double-masked, multi-country clinical trial compared the efficacy and safety of emedastine 0.05% bid and levocabastine 0.05% bid. Economic comparison of a strategy with Emedastine, and a strategy with Levocabastine, including first line therapy and failure’s therapy was modelled using clinical trial results and standard cost approach. Societal perspective was adopted unless no indirect costs were estimated. Only drug costs were considered for first line treatment costs. The costs of failure were established from a panel of Ophthalmologists and General Practitioners and focused mainly on out-patient resource utilization: visits, drugs, lab tests, etc. RESULTS: A total of 221 patients (109 emedastine, 112 levocabastine) presenting with allergic conjunctivitis were followed over 42 days. From day 7 to day 42, emedastine-treated patients had less itching (P<0.001) and less redness (P<0.001). The first line treatment failure rate was 10% less (P<0.02) in emedastine-treated patients and they had an incremental 8.5 days (P<0.01) without symptoms. Emedastine was as safe as levocabastine and well tolerated. Emedastine strategy was found economically dominating relative to levocabastine, i.e. less costly, and more efficacious, in Germany, Portugal and Sweden. In France, Belgium, the Netherlands and Norway less than one € per extra day free of symptoms has to be paid. Sensitivity analyses were conducted which confirmed the robustness of our findings. CONCLUSION: Based on results of a randomized clinical trial, and resources and costs associated with failure having been estimated through expert interviews, our model found that emedastine is a cost-effective alternative in the treatment of allergic conjunctivitis.