This 3-week prospective, randomized, double-masked, parallel-group study compared ketotifen fumarate 0.025% ophthalmic solution and olopatadine hydrochloride 0.1% ophthalmic solution in 66 patients with seasonal allergic conjunctivitis. The drugs were instilled twice daily. Signs and symptoms were assessed on days 5 (visit 2) and 21 (visit 3). Other efficacy variables were the responder rate (patients with excellent or good global efficacy on days 5 and 21) and patient and investigator ratings of global efficacy. Comfort was evaluated immediately after instillation of the first drop and at each follow-up visit. The frequency of adverse events was the safety assessment. The responder rate was higher with ketotifen than with olopatadine on day 5 (72% vs 54% for patient assessment, 88% vs 55% for investigator assessment) and day 21 (91% vs 55%, 94% vs 42%). Global efficacy ratings were higher with ketotifen, and severity scores for hyperemia and itching were significantly lower. Both drugs elicited comparable comfort ratings. The most common adverse events were burning/stinging and headache.