The prophylactic action of cyclandelate was investigated in a multicentre, randomized, placebo-controlled, parallel group study. A 4-week baseline period was followed by a 4-week placebo phase and a 16-week treatment period with either 1600 mg cyclandelate or placebo. Patients (n = 251) with two to six migraine attacks/month were randomized. Neither the primary study endpoint (reduction of migraine days from baseline to the last 28 days) nor most of the secondary endpoints (reduction in the number of migraine attacks, severity or duration of attacks, frequency of autonomic disturbances, medication for treatment of attacks) showed a difference between cyclandelate and placebo. Cyclandelate, however, was superior to placebo in a global impression of efficacy rated by the patients and the treating physicians. Both treatments were well tolerated. In conclusion, cyclandelate was not superior to placebo in the prophylaxis of migraine with regard to parameters usually used in migraine prophylaxis trials.