OBJECTIVES: Schizophrenia is a chronic disorder that requires long-term treatment with antipsychotic medication to minimize relapse and provide benefit to patients. Due to the long duration of treatment, adherence is an important factor in order to avoid relapses and re-hospitalization. Long-acting Injectable (LAI) formulations of atypical antipsychotics provide constant medication delivery and thus a potential improve in adherence. The aim of this analysis is to assess the cost-effectiveness of paliperidone palmitate (PP) relative to olanzapine (OP), quetiapine (QP) and ziprazidone (ZP) under the Brazilian Private Healthcare System perspective. METHODS: A decision-analytic Markov model was developed adopting a monthly cycle length. Patients entered the model according to three different adhesion states related to each treatment drug - fully compliant, partially compliant and non-compliant – and could subsequently transition between different health states during each monthly cycle. Probability of relapse, level of adherence, treatment discontinuation and adverse events associated with each intervention were sourced from literature and while resource use was obtained from specialist’s opinion. Costs and outcomes were evaluated over a 5-year horizon, and discounted at 5.0%. Exchange rate (1 USD = 2.30 BRL) Results were presented as incremental costs/relapses avoided. Deterministic and probabilistic sensitivity analyses were performed RESULTS: Total costs (USD): PP (15,917), OP (13,670), QP (16,845) and ZP (13,273). Hospitalization relapses costs (USD): PP (3,114), OP (4,504), QP (6,305) and ZP (6,459). Relapses rate: PP (1.15), OP (1.67), QP (2.37) and ZP (2.41). Incremental cost per relapses avoided (USD/relapses avoided): PP vs. OP (2,247), PP vs. QP (-927), PP vs. ZP (2,644).  CONCLUSIONS: Compared with the drugs under analysis, PP demonstrates savings in terms of hospitalization costs. Additionally, PP is a cost-saving strategy compared to QP and when compared to OP and ZP, is a cost-effective therapy for the treatment of schizophrenia in adults patients in Brazil.