OBJECTIVES: Evaluate the tolerability of three antipsychotic drugs – asenapine, iloperidone and lurasidone – in the treatment of schizophrenia. METHODS: An eletronic search was performed in Medline (Pubmed), Cochrane Library, Scopus, Science Direct and Scielo. A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the use of any of the above-mentioned drugs versusplacebo in schizophrenia was realized. Publications available in English, Portuguese, Spanish, French and German were evaluated. The main outcome was tolerability related to the number of withdrawals patients in each study, due to the presence of adverse events or treatment failure. The analyses were performed using software Addis (v.1.16.5) and RevMan (5.1). RESULTS: A total of 979 documents were initially identified and 11 of them met the selection criteria to meta-analysis. No significant differences were observed between the number of withdrawals patients due adverse events in any meta-analysis of control versus intervention. The odds ratio ranged from 0.68 (CI 032-1.45) to placebo versus asenapine, 1.37 (CI 0.29-1.33) to placebo versus iloperidone and 0,71 (CI 0,36-1,41) to placebo versus lurasidone. However, all drugs were superior to their respective controls for the outcome of number of withdrawals by treatment failure, with odds ratio between 1.70 (CI 1.21-2.39) and 2.36 (CI 1.36-4.07). These results suggest that there is a higher effectiveness among patients for the treatment intervention that should be evaluated through clinical responses. Heterogeneity between studies (evaluated by Ivalues) were low or moderate, not superior than 39,5% in any meta-analysis.  CONCLUSIONS: Information and knowledge reunion and confrontation on the tolerability profile of a particular drug allows safer decisions over the therapeutic approach, focused on patient’s interest which directly reflects on treatment follow-through and therapy effectiveness. In this study, we report evidence on asenapine, iloperidone and lurasidone greater tolerability profile compared to placebo in schizophrenia treatment.