OBJECTIVE To compare the efficacy of diclofenac sodium (DS) 0.1% and fluorometholone (FL) 0.1% in patients with perennial allergic conjunctivitis. METHODS Fluorometholone 0.1% or DS 0.1% eye drops were topically administrated 4 times daily for 4 weeks in patients with perennial allergic conjunctivitis. Assessment was conducted with a 4-point rating scale (0=none, 1=mild, 2=moderate, and 3=severe) for 4 signs and 5 symptoms. RESULTS Two hundred sixty-one patients were recruited. The demographics and baseline skin prick scores between both groups were comparable. Mean baseline scores in DS and FL group were 6.77 ± 2.24 and 6.34 ± 2.10, respectively. The scores rapidly decreased to 3.28 ± 1.47 and 2.69 ± 1.44 on day 7. Diclofenac sodium expressed a slower effect compared with FL within the first 3 days of treatment (P=0.01). CONCLUSIONS The efficacy of topical FL and DS was comparable for the management of cases with perennial allergic conjunctivitis. However, FL led to a more rapid alleviation of signs and symptoms as compared with DS in early days after the initiation of treatment.