OBJECTIVES: To evaluate the cost-effectiveness of Risperidone long-acting injection (LAI) in schizophrenia treatment. METHODS: We searched medical literature using key words risperidone, long-acting, cost-effectiveness, pharmacoeconomics and economic evaluation in Medline, Embase, Elsevier and Ovid databases up to January 2012. Literature review studies were excluded from this review. RESULTS: Twelve primary study articles were indentified and included in this review of which 2 in Germany, 2 in Sweden, 1 in US, 1 in France, 1 in Belgium, 1 in the UK, 1 in New Zealand, 1 in Canada, 1 in China Mainland, 1 in Taiwan. All studies only calculated the direct costs of treatments, including hospitalizations, medications, and consultations. Ten studies showed cost savings while the rest 2 studies concluded Risperidone LAI was more cost-effective than comparators.  Among the 10 studies showing cost savings, 4 studies further demonstrated better efficacy of Risperidone LAI than oral psychotics and Haloperidol long-acting injection, 4 studies showed a range of 0.22-0.55 relapses reduction with Risperidone LAI treatment resulting in significant cost savings, 2 studies showed a 0.043-0.103 QALY gained per patient in 5 years with Risperidone LAI, 3 studies compared the inpatient days and hospitalization frequencies before and after using Risperidone LAI with fewer inpatient days and hospitalizations after Risperidone LAI treatment.  Among the 2 studies showing Risperidone LAI was more cost-effective, the study in China Mainland showed Risperidone LAI was more cost-effective than Olanzopine and Quetiepine while the study from Taiwan found Risperidone LAI was more cost-effective than Olanzopine and depot haloperidol. CONCLUSIONS: Based on the available studies, this systematic review found that Risperidone LAI was a cost-effective treatment for schizophrenia patients.