Abstract: Inflammation is thought to play a significant role in the underlying pathophysiology of migraine headaches which could be controlled by corticosteroids. The present study was conducted to determine and compare the pain relieving effect of dexamethasone versus morphine on patients with acute migraine headache. During this double blinded clinical trial study, 190 patients who met the International Headache Society definition of acute migraine headache were evaluated at emergency department of Tabriz Imam Reza Hospital. After giving informed consent, patients were randomly enrolled into two groups: Receiving either 8 mg dexamethasone (group A) or 0.1 mg kg-1 morphine (group B) intravenously. Severity of the headache was determined using Visual Analog Scale (VAS) scoring method at baseline (VAS-A), 10 min (VAS-B), 60 min (VAS-C) and 24 h (VAS-D) after intervention. The mean age of patients was 44.17±16.20 years, 61.57% male and 38.43% female. The mean of VAS-A and VAS-B scores was not statistically different between two groups (p = 0.236 and p = 0.481), but the mean of VAS-C and VAS-D scores in the group A were significantly lower than the group B (p = 0.017, p = 0.010). In long-term (1 h and 24 h after administration), dexamethasone reduces the severity of acute migrant headache more than morphine.