OBJECTIVES: Paliperidone ER is a second-generation antipsychotic drug developed by Johnson & Johnson Pharmaceutical Research and Development, L.L.C. as a new therapeutic agent for the treatment of schizophrenia. This study aims to evaluate the cost-effectiveness of paliperidone ER compared to other oral atypical hotics (risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) using health economic modeling techniques. METHODS: The target patients population is patients with schizophrenia who have suffered an acute exacerbation of illness . The setting of care is outpatient. We suppose that there are six alternate pharmacologic options: (1) paliperidone ER ; (2) risperidone; (3) olanzapine; (4) quetiapine; (5) ziprasidone; or (6) aripiprazole. The analysis is from the 3rd party payer perspective. Two time horizons are available for the schizophrenia cost-effectiveness model: 6-weeks (acute treatment model) and 1-year (long-term treatment model). Patients who respond at six weeks may either continue to one year or discontinue prior to the end of the year. RESULTS: The base case analysis showed that paliperidone ER except risperidone is more effective and less costly than the comparators over a 1-year time horizon. A 1-year cost per patient with paliperidone ER costs Korea Won KRW4,037,612, while that with risperidone costs KRW3,844,438. The average gain in symptom-free stable day attributed to paliperidone ER treatment compared to risperidone treatment was 1.4615 days (=340.6467 – 339.1822). Therefore, incremental cost per stable day was KRW131,905.CONCLUSIONS: The economic evaluation indicates that, given a wide range of assumptions, the increased cost of treating patients with schizophrenia with paliperidone ER may be partially offset by a reduction in other direct medical costs, as a consequence of an increase in the number of stable day.