We undertook a double-blind, placebo controlled study to determine the effectiveness of fenoprofen calcium in the prophylaxis of migraine. One hundred and ten patients were treated with fenoprofen 200 mg. TID (35 patients), fenoprofen 600 mg. TID (39 patients), or matching placebo (36 patients), for 12 weeks, following a four week placebo baseline phase. Migraine frequency, severity, duration, and need for relief medication were recorded using headache diaries. Greater than 50% improvement in headache unit index was observed in 22% of patients on fenoprofen 200 mg. TID (p<0.05) and 36% of patients on fenoprofen 600 mg. TID (p<0.005). Fenoprofen 600 mg. resulted in 50% or greater reduction in corrected headache unit index in 59% of patients (p<0.005) and relief medication index in 55% (p<0.001), Gastrointestinal side effects were reported in 13.5% of patients, and fatigue was noted in 4% of patients treated with fenoprofen 600 mg. TID. We conclude that fenoprofen is safe and effective in the prophylaxis of migraine.