OBJECTIVES: To assess the comfort and efficacy of epinastine 0.05% ophthalmic solution in contact lens wearers with a history of allergic conjunctivitis and contact lens intolerance during allergy season. METHODS: One hundred forty-six subjects were enrolled in a multicenter, open-label study. Enrolled subjects instilled rewetting drops twice a day for a one-week run-in period, then were randomized to epinastine 0.05% twice a day plus rewetting drops as required (n = 75) or rewetting drops alone as required (minimum use twice a day) (n = 71). Subjects recorded the length of time that contact lens wear was comfortable, the total time of wear, ocular itch, overall comfort, and use of rewetting drops during the run-in period, at baseline, and on days 2 to 7 of the treatment period. RESULTS: Subjects averaged 34 years of age; 79% were female. No significant differences were shown at baseline between subjects treated with epinastine 0.05% twice a day plus rewetting drops and control subjects treated with rewetting drops alone. Averaged over the treatment period, epinastine provided significant increases in comfortable wearing time (1.33 ± 2.89 vs. 0.43 ± 2.28 hr, P=0.012) and total wearing time (0.35 ± 1.87 vs. -0.32 ± 1.81 hr, P=0.008) compared with controls. Epinastine users reported less frequent additional rewetting drop use on average by 0.56 uses per day, which was significantly different than controls (reduction of 0.06 uses per day; P=0.012). Epinastine provided significantly greater improvements from baseline in ocular itch and overall eye comfort compared with rewetting drops alone (P≤0.001). CONCLUSIONS: Epinastine 0.05% may be useful for the treatment of seasonal allergic conjunctivitis in contact lens wearers. © 2009 Lippincott Williams & Wilkins, Inc.