Today, despite of the improvement in the psychological therapeutic approach, mania still remains as a challenging problem for health system. The aim of this study is comparison efficacy of risperidone and aripiprazole in combination with sodium valproate in bipolar patients with acute manic or mixed episodes who hospitalized in Razi psychiatric hospital in Tehran. This study was conducted as a double blind randomized clinical trial in two groups of bipolar disorder patients with manic or mixed episodes (18–65 age). Patients randomly set in two groups who received valproate with aripiprazole or risperidone. Clinical response was assessed with young mania rating scale (YMRS) and weight gain at 3 and 6 weeks. Data was analyzed with Chi2 test, paired t-test and analysis of covariance and repeated measurement. Evaluation of treatment response after 3 and 6 weeks (50% reduction in Young's scale) in both groups did not show any significant difference between the two therapeutic combinations. The combination of sodium valproate and risperidone showed higher weight gain in comparison with the combination of valproate and aripiprazole at the end of week 6 (P < 0.001). The mentioned combination in bipolar I disorder with manic or mixed episode has similar therapeutic effect, so that both of them are effective and usable. There was no difference in their efficacy, and both treatments can be used. Due to the less weight gain, the combination of valproate and aripiprazole in patients who prone to weight gain, this approach is recommended as more safe and effective therapy.