OBJECTIVES To quantify the economic burden of schizophrenia relapse in Brazil, and to estimate the impact of atypical Long Acting Injectables (LAIs) on relapse. METHODS Administrative health service data from a Brazilian public system database (DATASUS) were used to estimate the number of relapse patients and related resource utilisation. Corresponding data for private system patients were estimated based on published literature and by extrapolating DATASUS data. A prevalence-based costing with a mixed bottom-up and top-down approach was used to quantify direct and indirect costs, disability adjusted life years (DALYS) and their associated monetary value. A decision-analytic model was constructed to evaluate the cost effectiveness of potentially transferring non-compliant patients from oral antipsychotics to atypical LAIs. All costs are presented in 2013 Brazilian real. RESULTS In 2011-12, 88,721 patients with schizophrenia in Brazil experienced 263,037 episodes of relapse that resulted in hospital or outpatient care. The potential avoidable healthcare cost of relapse was R$722.6 million. The estimated additional healthcare cost per DALY avoided was R$5,049 if non-compliant patients could be transferred to atypical LAIs to achieve 5% overall utilisation. Reducing relapses would give Brazil potential avoidance of 1,335 DALYs, which corresponds to a saving of R$482.8 million in the stock of health capital. CONCLUSIONS The economic burden of schizophrenia relapse in Brazil is significant. Brazilian policymakers should provide greater access to LAIs.