Headache occurs in sickle cell disease (SCD), but its characteristics and frequency have not previously been studied. Our aim was to study patterns of headache in adults with SCD and to correlate its presence with blood flow velocities measured by transcranial Doppler (TCD) and with brain magnetic resonance imaging (MRI) abnormalities. We studied 56 adults with SCD. Twenty-eight patients (50%) had severe and frequent headaches. In 20 patients (35.7%) the headache met the International Headache Society criteria for migraine without aura. Patients with frequent and severe headache presented TCD velocities significantly higher than those without headache, or with milder headache. No correlation was found between headache and abnormalities in brain MRI. A migraine-mimicking headache occurs in SCD but we should not understand it as a primary headache because the blood flow abnormalities secondary to SCD detected by TCD seem to play an important role in these patients.