In this 2-week, randomized, crossover study, ophthalmic solutions of nedocromil sodium 2% and olopatadine hydrochloride 0.1% were compared for effectiveness and acceptability in 28 patients with perennial allergic conjunctivitis and previous olopatadine experience. Patients received nedocromil twice daily or olopatadine twice daily for 1 week, then were crossed over to the alternate medication for 1 week. Outcome measures were patient satisfaction (questionnaire), severity of ocular symptoms (daily diary scores), clinical signs (physician assessments), quality of life (questionnaire), and global assessments of effectiveness. Both medications were well accepted. Of the 28 patients, 16 (57.1%) would request a nedocromil prescription, 10 (35.7%) an olopatadine prescription (P = .157); 22 patients (78.6%) would recommend nedocromil to other allergy sufferers, while 18 (64.3%) would recommend olopatadine (P = .480). Light sensitivity scores were significantly lower with nedocromil (P = .0125); other symptom scores were comparable between medications. Both drugs significantly (P < .01) and comparably decreased erythema, conjunctival injection, and overall conjunctival signs from baseline. Comparable improvement also occurred in quality-of-life scores. Both physicians and patients judged nedocromil and olopatadine to be similarly effective in preventing signs and symptoms. Nedocromil sodium 2% is an effective treatment for perennial allergic conjunctivitis. Patients receiving olopatadine can be switched to nedocromil with no loss in efficacy or satisfaction, but with a reduction in cost.