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Paliperidone may be effective for the treatment of bipolar disorder (BD); however, the evidence has been mixed. This is the first meta-analysis to evaluate the efficacy, safety, and tolerability of paliperidone for the treatment of BD. We performed a systematic search of the literature using major electronic databases from inception to January 27, 2017. Randomized control trials (RCTs) investigating paliperidone treatment among patients with BD versus a placebo or other second-generation antipsychotics were included. We then performed exploratory random-effects meta-analysis. The 3 included RCTs compared paliperidone with placebo (667 patients received paliperidone and 369 received a placebo). The dose of paliperidone in the included studies ranged from 3 to 12 mg/day. Paliperidone did not significantly improve manic symptoms (Hedges’ g = −0.221, p = .067, k = 5) compared with a placebo; however, it was superior to a placebo in improving psychosocial function (Hedges’ g = −0.156, p = .042, k = 3) and general severity (Hedges’ g = −0.205, p = .001, k = 5). Paliperidone was associated with a greater use of anticholinergic medications (p = .002), increased body weight (p < .001), and higher serum prolactin level (p < .001) compared with a placebo. Our preliminary results suggest that paliperidone does not offer significant benefits for the treatment of mania symptoms in BD compared with a placebo. In addition, treatment with paliperidone was associated with a higher incidence of adverse effects. Because of the limited number of studies, further well-designed RCTs are warranted.