OBJECTIVES: Schizophrenia patients who suffer from frequent relapses have their cognition damaged and need heavy medical resource utilization such as long-term hospitalization. Schizophrenia incurs a burden not only to patients and caregivers, but also to society. This study aims to carry out cost-utility analysis of ‘paliperidone palmitate long acting injection (PLAI)’ that improves drug adherent compared with atypical oral antipsychotics (risperidone, olanzapine, aripiprazole and paliperidone) from a payer’s perspective. METHODS: The study subjects are non-adherent schizophrenia patients with exacerbation of symptoms. A decision-tree model was constructed to compare the clinical and economic outcomes of PLAI and oral comparator over 1 year. Clinical data such as relapse rate, EPS rate, suicide rate and non-adherent rate as well as utility weight were obtained from published literature. Direct medical cost data were also obtained from a domestic literature. Sensitivity analyses were performed on PLAI drug cost and major variables. RESULTS: : Based on model estimates, PLAI showed some advantages of reducing hospitalization and increasing utility over its comparators. Total direct medical costs were KRW 5.62million for PLAI, and KRW 4.71million for comparators. Incremental cost-effectiveness ratio of PLAI versus oral atypical antipsychotics was KRW 2.22million per quality-adjusted life year (QALY). Sensitivity analyses showed that hospitalization cost per day and frequency of hospitalization per year had greatest influence on the result. CONCLUSIONS: The use of PLAI may result in improved health effect and QALY compared with atypical antipsychotics. Despite its higher cost, PLAI can be considered as one of the options for non-adherent patients in schizophrenia, as it reduces hospitalization and increases quality of life.