Studies of postmortem brain tissue are advancing the understanding of the pathophysiology of major depressive disorder (MDD). The nature and quality of subject samples, however, limit their applicability to late-life MDD. To examine the feasibility of establishing a brain bank for late-life MDD, and identify clinical, demographic, and procedural factors that might facilitate subject enrollment. Elderly subjects participating in clinical trials associated with the Mental Health Intervention Research Center for Late-Life Mood Disorders (MHIRC/LLMD) at the University of Pittsburgh were approached by clinical research staff for consent to future brain-only autopsy. Subjects who consented to participation were compared with those who refused participation on demographic and clinical variables. MHIRC/LLMD clinical research staff were interviewed to determine factors that may have facilitated or hindered the consent process and reasons for subject consent or refusal. Eighty out of 242 subjects (33%) subjects approached for participation in the brain bank provided consent. Consent to participate was associated with higher level of education and with lower Mini-Mental State Examination score. Several factors facilitating and hindering the consent process were identified. We provide preliminary evidence for the feasibility of establishing a brain bank for the study of late-life MDD. Future efforts may be guided by the factors identified as facilitating the consent process, especially the inclusion of family in the consent process.