Objective To investigate treatment effect of prednisone to withdrawal headache in patients with medication overuse headache (MOH). Methods From June 2009 to June 2013, 96 patients with MOH were chosen as study objective for the randomized double-blind and placebo controlled study.All patients were divided into 2 groups: 48 in study group ( treated with prednisone, 100 mg/d ) and 48 in control group (treated with placebo, 100 mg/d).The clinical features of two groups were compared.After treatment, the primary endpoints, secondary endpoints , further results and the use of analgesics were compared.Results Before treatment, the age, sex gender,primary diagnosis, duration and frequency of headache, medicine had no statistical difference between two group.After treatment, the duration of headache and the rate of drug rescue had no statistical difference between two groups.The rate of withdraw symptoms had no statistical difference between two groups.The use of analgesics was less in study group than that in control group, the difference had statistical significance (P<0.05).Conclusion During withdrawal in MOH, prednisone reduces rescue medication without decreasing the severity and duration of withdrawal headache.