OBJECTIVES To compare the treatment cost of paliperidone palmitate (PP) versus risperidone long acting (R-LA), both indicated for the treatment of schizophrenia in Brazil. METHODS In Brazil, both (PP and R-LA) long acting 2^nd generation antipsychotics are approved for the treatment of schizophrenia. Published literature shows no difference in safety and efficacy between them; therefore, a cost-minimization analysis was performed. Yearly treatment costs were calculated for an average dose of 37,5 mg per patient in the case of R-LA and 75 mg in the case of PP. The two initial treatment doses were considered: for PP, 150 mg on the 1^st day and 100 mg on the 8^th day, and for R-LA 21 days oral supplementation with 3 mg of risperidone, according to dosing intervals defined in the product label. Prices were gathered from the official price list (CMED – Apr’14). RESULTS PP has the lowest cost of treatment, at R$ 12,739 per patient in the 1^st year – against R-LA R$ 18,165 – and R$ 11,359 in the 2^nd year (R-LA has R$ 17,971). Treatment with PP compared to R-LA may bring important savings to the payers (HMOs or Government), with potential to reduce the cost of treatment by 30% in the 1^st year, and 37% in the 2^nd year - allowing a higher number of patients to be treated at the same budget level. CONCLUSIONS Although both molecules, PP and R-LA, have demonstrated similar efficacy, PP offers a cost reduction from the perspective of the Brazilian private health care system compared to R-LA. In addition, PP offers advantages that can have additional value for public and private payers alike such as a monthly injection and no need for cold chain. PP can therefore be considered a cost-saving therapeutic option for schizophrenia compared to R-LA.