OBJECTIVES: To determine and compare the compliance and persistence to typical and atypical antipsychotics in the treatment of schizophrenia patients. METHODS: The study was based on NC Medicaid claims database. Patients were included if they had a diagnosis of schizophrenia (ICD-9 295.xx), received at least two antipsychotic prescriptions during the period after index date and were continuously enrolled in NC Medicaid Program during three month prior and one year post treatment periods. Medication possession ratio (MPR), persistence and medication use gap were used as compliance measures. Both descriptive and multivariate model were conducted to determine the difference in adherence/persistence to antipsychotic medications between typical and atypical antipsychotic. RESULTS: A total of 919 patients (469 in typical and 450 in atypical) met the selection criteria for 3-month prior and 12-month after antipsychotic treatment. There were statistically significant differences between typical and atypical antipsychotics in terms of demographics, comorbidities, resource utilization in prior period, and adherence. As compared with those in typical groups, patients in atypical group were significantly younger (42.3 vs. 44.4, p=0.0195), less blacks (33.1% vs. 58.4%), had more comorbid diseases (2.7 vs. 2.3, p=0.0025), more hospital visits (0.3 vs. 0.17, p=0.002) and greater total costs in prior period ($2703 vs. $2010, p=0.012). The costs and utilization in prior period indicated that patients in atypical groups were sicker than those in typical groups. Patients in atypical group were more adherent to antipsychotics (35.8% vs. 16.4%, p<0.0001), less gaps (42.4% vs. 67%, p<0.0001), and stayed consistently in medication longer (229 days vs. 146 days). CONCLUSIONS: The results from this study indicated that there existed significant differences in terms of demographics, compliance and persistence between typical and atypical antipsychotics in the treatment of schizophrenia.