Mixed states are common and severe manifestations of bipolar disorder, with limited data on the differential efficacy of treatments on depressive and manic symptoms. This study assessed the effectiveness of open-label adjunctive risperidone in achieving sustained effectiveness in patients with mixed mania, with a specific focus on the differential benefits on manic and depressive symptomatology. Forty patients with bipolar disorder I, currently in a mixed manic episode, were treated with adjunctive risperidone. Behavioral measures at baseline and weeks 1, 2, 4, 8, 12, 16, and 20 were assessed using the following scales: the Young Mania Rating Scale, the Montgomery Asberg Depression Rating Scale (MADRS), and the Global Assessment Scale. The primary outcome measure was the proportion of patients who attained a sustained response on either depressive or manic symptomatology, defined as at least 50% reduction from the baseline on the Montgomery Asberg Depression Rating Scale or the Young Mania Rating Scale, maintained over at least 8 weeks without subsequent relapse during the 20-week trial. A significantly higher proportion of patients achieved a sustained response for mania than depression, 16/40 versus 6/40, respectively (McNemar’s χ 2 8.33, P=0.004). Higher elevated mood at baseline and lower apparent sadness (P<0.016) each predicted a sustained response for mania (P<0.0001). Mixed manic patients who were treated with risperidone adjunctive to mood stabilizer/s for 20 weeks were significantly more likely to achieve a sustained response for manic than for depressive symptomatology.