The aim of this study is to assess, in a double blind randomized clinical trial, the effect of chlorpromazine (CPZ) on the pain and associated symptoms in patients with migraine. Sixty patients with migraine with aura and 68 patients with migraine without aura were assigned at random to receive IV 0.1 mg/Kg CPZ or placebo. We assessed pain intensity, nausea, photophobia, and phonophobia at baseline, 30 min, and 60 min post-IV administration. End-point efficacy at 60 min was used to calculate the number needed to treat (NNT). We also recorded adverse effects, need for rescue medication at 24 h, and recurrence of headache at 24 h. We found clinically and statistically significant (p < 0.01) improvement associated with CPZ in pain scores, nausea, photophobia, phonophobia, and need for rescue medication, all at 60 min, and in rate of recurrence at 24 h, both in patients with and without aura. NNT = 2. Those allocated to CPZ had less nausea and dyspepsia, but more drowsiness and postural hypotension than those receiving placebo. CPZ is an excellent option for the treatment of migraines, with and without aura, in the Emergency Department.