Objective.-To investigate the effect of low-intensity acenocoumarol treatment (target INR 1.5 to 2.0) on the frequency and severity of migraine attacks.Background.-The positive effect of anticoagulation on migraine has been described in case reports and observational studies.Methods.-We conducted a randomized, open, crossover study in migraine patients. After a run-in period of 8 weeks, all patients received acenocoumarol or propranolol during a period of 12 weeks and, after a washout period of 2 weeks, propranolol or acenocoumarol during a second period of 12 weeks.Results.-Nineteen patients fulfilling the criteria were included. In 12 patients with complete data collection, only one good responder could be noted. In the other patients, treatment with low-intensity acenocoumarol did not show improvement of migraine symptoms compared with the run-in period. Treatment with propranolol showed a trend towards improvement compared with the run-in period. No serious adverse events were observed.Conclusions.-Overall, low-intensity acenocoumarol treatment has no prophylactic effect in migraine patients.Key words: migraine, anticoagulation, acenocoumarol, migraine prophylaxis (Headache 2005;45:137-143) The drugs recommended for prophylactic therapy of migraine show a limited effectiveness and a great interindividual variability. In addition, some of these drugs may cause troublesome, sometimes severe, adverse effects, which can contribute to noncompliance.