OBJECTIVES: Mortality among schizophrenia patients is higher than the general population. Antipsychotics are the mainstay of schizophrenia treatment but have been linked to life threatening adverse events. Therefore the objective of the study was to systematically review available literature examining the risk of mortality associated with antipsychotic  use  among schizophrenia patients. METHODS: Systematic review of English literature was conducted in MEDLINE, PubMed, PsychInfo, EMBASE, Cochrane databases, and IPA from 1966 to October 2011 using nine element eligibility criteria to identify studies examining the association between antipsychotic use and mortality. The primary inclusion criteria involved diagnosis of schizophrenia, exposure to antipsychotics, at least one year follow up, and ascertainment of mortality. Findings from case-control, cohort, and controlled trial studies were abstracted for evidence table preparation and possible meta-analyses. RESULTS: Overall sixteen studies were included after employing nine element eligibility criteria. The studies were heterogeneous in terms of study designs; follow up period, and control of selection bias and confounding.  Consequently meta-analysis was not conducted. Nine out of sixteen studies concluded increased risk of mortality among antipsychotic users compared to non-users. Three out of four studies examining the antipsychotic polypharmacy found significant positive effect on mortality. One out of two studies examining the compliance with antipsychotics found negative effect on mortality. One out of two studies examining association of antipsychotic dosages found significant association with increased mortality. One study ascertained stable association with antipsychotic treatment intensity and increased cardiovascular mortality while other found no significant association. The follow up period varied from 1 to 17 years. Prospective studies controlled for lifestyle related factors while retrospective studies for some comorbidities and co-medications. CONCLUSIONS: Literature review revealed that antipsychotic use and antipsychotic polypharmacy increased the risk of mortality. Well designed observational studies accounting for selection bias and confounding are needed to establish the relationship.