Objective: To assess long-term outcome in bipolar disorder, subjects were prospectively followed after receiving acute treatment for bipolar depression. Method: Eighty-three outpatients with DSM-IV bipolar depression who were enrolled between March 1996 and November 2002 and were treated in a 10-week acute double-blind antidepressant treatment trial agreed to participate in a 1-year double-blind continuation of their medication. In the acute antidepressant treatment trial, subjects were treated with a mood stabilizer plus 1 of 3 randomly assigned antidepressants. Sixty-one subjects had attained an acute positive antidepressant response (50% improvement on the Inventory for Depressive Symptomatology [IDS] or 2-point improvement on the Clinical Global Impression for Bipolar Disorder [CGI-BP]) and 22 subjects achieved only acute partial improvement at the end of the 10-week acute trial. In the blinded continuation phase immediately following the acute trial, subjects continued on the same medications and were rated monthly for up to 1 year using the IDS, CGI-BP, and the Young Mania Rating scale. Results: At study endpoint, 42 (69%) of the 61 acute positive responders maintained positive response and 32 (53%) achieved remission. Compared to the acute positive responders, 6 (27%) of the 22 acute partial responders had achieved positive treatment response at study endpoint (p < .001). Eight acute positive responders (13%) and 5 acute partial responders (22%) developed mania. Conclusion: Patients who achieve a positive acute antidepressant response to 10 weeks of antidepressant treatment adjunctive to a mood stabilizer will probably maintain response with the same continued treatment. Patients who achieve only a partial acute antidepressant response are less likely to further improve when the same treatment is sustained. The switch rate into mania for patients being treated with an antidepressant adjunctive to a mood stabilizer is not higher than the reported rate for patients on mood stabilizer monotherapy. © Copyright 2009 Physicians Postgraduate Press, Inc.