Background & Objective: Pizotifen is an alternative option for prophylactic treatment of migraine headache. This study aims to compare the effi cacy and safety of pizotifen with sodium valproate; one of the most-widely used drugs in migraine prevention. Methods: This was a single blind, randomized, parallel-group study. After a 4-week baseline evaluation, patients with episodic migraine were randomly assigned to get either sodium valproate or pizotifen for a period of 12 weeks. Patients were asked to fi ll a headache diary through the study. Headache characteristics and the possible side effects were evaluated throughout and at the end of trial. Results: Forty two patients aged 20 to 49 were recruited to the study. With both drugs, the frequency, intensity and duration of headaches were signifi cantly reduced (p < 0.05). Except for headache duration, pizotifen was signifi cantly superior to sodium valproate in the headache parameters assessed. Total reported side effects were initially higher in patients who received pizotifen (37 vs. 22; P= 0.038); however, persistent side effects were lower for pizotifen (6 vs. 10; P= 0.22). Conclusions: The results of this study suggest that pizotifen is a safe and effective drug in migraine prevention.