Headache centers have to deal with patients suffering from headache induced by chronic substance use which is a well-recognized complication of migraine treatment. The objective of this study was to compare psychiatric comorbidity between migraineurs with and without chronic substance use: 34 migrainous inpatients with chronic substance use were compared with 34 sex-matched noncomplicated migraineurs in a case-control study. The results showed a significantly higher prevalence of major depressive disorder, panic disorder, and social phobia in the patients with a history of chronic substance use. Consistently, anxious and depressive dimensions were significantly higher in these patients. Therefore, psychiatric morbidity may be linked to chronic substance use in migraineurs. This stresses the importance of psychiatric assessment and the need for appropriate treatment in such patients.