OBJECTIVE Outcome studies have previously documented substantial functional disability among individuals with bipolar disorder, although few follow-up studies have examined the prospective course of illness beyond 10 years' duration. METHODS A total of 95 patients with mood disorders (46 with bipolar I disorder and 49 with unipolar nonpsychotic depression) were assessed 15 years after index hospitalization. Logistic and linear regression models were used to identify predictors of global functioning, work disability, and social adjustment. RESULTS At 15-year follow-up, good overall functioning was significantly less common among subjects with bipolar disorder (35%) than unipolar depression (73%) (p<0.001). Work disability was significantly more extensive in bipolar than unipolar disorder subjects (p<0.001). Logistic regression indicated that good outcome 15 years after index hospitalization was significantly predicted by a unipolar rather than bipolar disorder diagnosis and the absence of a depressive episode in the preceding year. Past-year depressive, but not past-year manic, syndromes were associated with poorer global outcome and greater work disability. In addition, subsyndromal depression was significantly associated with poorer global, work, and social outcome among bipolar, but not unipolar disorder subjects. CONCLUSIONS A majority of individuals with bipolar I disorder manifest problems with work and global functioning 15 years after an index hospitalized manic episode Recurrent syndromal and subsyndromal depression disrupts multiple domains of functional outcome more profoundly in bipolar than unipolar mood disorders. The prevalence, and correlates, of impaired long-term outcome parallel those reported in shorter-term functional outcome studies of bipolar disorder.