Background & Objective: There is a need for a more effective and better tolerated prophylactic treatment of migraine. This study aims to compare the effi cacy of botulinum toxin type-A (Dysport) and divalproex sodium (divalproex) as prophylactic treatment in patients with episodic or chronic migraine. Methods: This was a randomized, cross-over, single-center clinical trial. Participants were randomly divided into two treatment groups. Two phases of intervention were arranged (each for three months). In the fi rst phase, patients received either Dysport (125 units) or divalproex (200 mg bid for three months). The patients were left for a three months washout period, and then the treatment agents were swapped in the second stage. The response to each treatment was assessed at the end of each phase. Results: With divalproex, the frequency, intensity and duration of headache, as well as analgesic consumption were signifi cantly reduced (p<0.05) in both episodic and chronic patients. However, Dysport demonstrated signifi cant effi cacy only in patients with episodic migraine. In chronic migraine, Dysport only showed a non signifi cant trend to benefi t in these parameters, with exception of headache intensity,where it resulted in signifi cant improvement from baseline. Divalproex was signifi cantly superior to Dysport, in terms of headache frequency and intensity in patients with episodic migraine. Conclusions: Both Dysport and divalproex are effective prophylactic therapies for patients with episodic migraine. Divalproex but not Dysport was signifi cantly effective for chronic migraine.