The aim of this study was to quantitatively review, using a meta-analytic approach, randomized-controlled trials analyzing the efficacy and safety profiles of asenapine in the treatment of bipolar disorder (BD). MEDLINE (1966 to August 2012) and EMBASE (1980 to August 2012) databases were systematically searched to identify relevant papers. Data from four randomized-controlled trials were analyzed. For continuous data (Young Mania Rating Scale, Clinical Global Impression Scale for Bipolar Disorder, and Montgomery-Asberg Depression Rating Scale scores), the Hedges g was adopted as a measure of the effect size; for dichotomous outcome measures (discontinuation and rates of adverse events), the risk ratio was calculated. In short-term trials, asenapine was found to be significantly superior to placebo in the treatment of manic symptoms of BD. There is also evidence of the positive effects of asenapine compared with placebo on depressive symptoms in mixed bipolar states. In the medium-term and long-term studies, asenapine showed comparable efficacy with the well-established comparator olanzapine in the treatment of manic and depressive symptoms of BD. Adverse events such as somnolence, weight gain, and extrapyramidal symptom, which have an impact on treatment adherence, are scarcely or moderately elicited by asenapine, which shows a better profile than olanzapine on metabolic parameters. On the basis of these results, asenapine can be considered as an effective and tolerable treatment for manic and mixed episodes of BD.