OBJECTIVES: Clinical trials have demonstrated the efficacy of atypical antipsychotic agents in reducing symptoms of schizophrenia. However, the likelihood of sustaining control of schizophrenic symptoms may depend on treatment persistence. In this study, we compared treatment persistence between patients who were initiated on risperidone or olanzapine, the two most widely prescribed atypical antipsychotic agents. METHODS: We identified patients with schizophrenia by ICD-9-CM codes (>1 inpatient or > 2 outpatient ICD-9-CM codes > 7 days apart) between July 1, 1998 and June 30, 1999. We further selected those who were prescribed the target drug during April 1, 1999 through March 31, 2000 provided that they were not on any antipsychotic agents during the prior six months. Using event history analysis, we compared treatment persistence in terms of hazard ratio between olanzapine and risperidone initiators, adjusting for patient sociodemographic and clinical characteristics. RESULTS: Following the initiation of the target drug, more patients switched from risperidone to olanzapine than visa versa. Olanzapine initiators had decreased hazards of discontinuation by 14% (unadjusted; p <0.001) and 12% (adjusted; p = 0.002), respectively, than risperidone initiators. CONCLUSIONS: Compared with risperidone, olanzapine seems to be better tolerated by patients as indicated by better treatment persistence. The initiation of olanzapine may thus increase the likelihood of sustaining control of symptoms of schizophrenia. Future research needs to provide a more comprehensive assessment of treatment persistence by considering other factors, such as formulary decision, and other antipsychotic agents in the study and developing models to assess treatment persistence and switching as two interdependent competing risks.