The anterior cingulate cortex (ACC) is involved in the regulation of emotion processing, and its volume has been found to be reduced in patients with major depression. Furthermore, larger ACC volumes have been associated with faster symptom improvement under therapy. The aims of the study were to examine whether volumes of the anterior cingulate cortex are altered and are related to the clinical course of major depression. Subjects comprised 78 inpatients with major depression and 78 age-, gender- and handedness- matched healthy volunteers, who were investigated with structural magnetic resonance imaging (MRI). The ACC was subdivided into the subgenual, pre-callosal, rostral-anterior and caudal-anterior ACC. No significant differences were observed for ACC volumes between patients and healthy controls. Left ACC volumes showed a significant negative correlation with the number of hospitalizations. These findings suggest that ACC volumes are not altered in patients with major depression, but that patients with larger ACC have a better clinical outcome than patients with smaller ACC.