Increasing evidence indicates that some second-generation antipsychotics are efficacious in bipolar depression, but there are few data on this illness for the novel agent aripiprazole.Aripiprazole response was prospectively assessed for 8 weeks with the Montgomery–Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale Modified for Bipolar Illness (CGI-BP), and the Young Mania Rating Scale (YMRS) in 31 bipolar patients with acute depression inadequately responsive to 1 mood stabilizer. Side effects and body weight were also evaluated. Outcome measures were analyzed with repeated measures ANOVAs.Patients showed a significant decrease in mean MADRS total and CGI-BP-Depression Severity scores, but only 14 (45%) completed the 8-week trial. Thirteen (42%) patients met criteria for response (≥50% reduction in MADRS total score), 11 (35%) patients met criteria for remission (final MADRS total score ≤12), and 9 (29%) patients discontinued aripiprazole for side effects, most commonly akathisia (N=4). As a group, patients showed statistically insignificant weight gain (0.8±2.5 kg) over the 8-week trial.Aripiprazole was associated with beneficial effects on mood in some patients with bipolar depression, but also had a high discontinuation rate, primarily due to side effects. Double-blind, placebo-controlled studies are necessary to determine aripiprazole's efficacy, tolerability, and safety in bipolar depression.