We examined factors related to social and occupational disability, social adjustment, and work disability among patients with major depressive disorder (MDD), the dominant mental disorder causing functional and work disability. The Vantaa Depression Study comprises a cohort of 269 psychiatric inpatients and outpatients with MDD in the city of Vantaa, Finland. Axis I and II diagnoses were assessed via semistructured WHO Schedules for Clinical Assessment in Neuropsychiatry Version 2.0 and Structured Clinical Interview for DSM-III-R personality disorders interviews. Global disability, social and work adjustment, and being at work or on sick leave were assessed. The most important factors associated with level of social, functional, and work disability were severity and recurrence of depression, but older age and current Axis I and II comorbidity also significantly contributed. Of those employed, almost half (43%) were on sick leave. The most pervasive factors explaining level of functional and work disability among patients with MDD were severity and recurrence of depression. However, older age and comorbidity also contributed.