OBJECTIVES: To assess switching of atypical and typical antipsychotics among stable and unstable patients and the relationship between switching and hospitalization. METHODS: We used data from the first year of a large (N=2327), 3-year non-interventional observational study of schizophrenia patients in the U.S, conducted between 7/1997 and 9/2003. Participants with at least one prescription for any antipsychotic were included in this analysis. Participants were defined as “stable” if they had PANSS total scores below 70 at enrollment and no psychiatric hospitalization, psychiatric emergency services, suicide attempt, or arrest in the 1-6 months prior to enrollment. All other participants were deemed “unstable.” Systematic medical record abstraction provided antipsychotic prescription information. The stable and unstable patient groups were compared on antipsychotic switching rates (switch from the antipsychotic used at enrollment) and on antipsychotic augmentation. Group comparisons were performed using t-tests for continuous variables and Chi-square tests for categorical variables. RESULTS: Of 2158 participants, 59.6% were deemed unstable and 40.4% were considered stable. Unstable patients were more likely to experience switching and augmentation of antipsychotics. Typical antipsychotics were more likely to be used as augmentors (58.7%, p<0.001), whereas atypical antipsychotics, especially olanzapine, were more likely the medications to be switched to (61.9%, p<0.001). A significantly higher proportion of switchers (44.6%) than non-switchers (17.9%, p <0.001) were hospitalized for psychiatric purposes during the 1-year observation period. Among switchers who were hospitalized at any time during the 1-year period, 52.4% switched medication during hospitalization, 29.8% switched prior to hospitalization, and17.8% switched post hospitalization. CONCLUSION: Switching of antipsychotics appears to be significantly associated with unstable, more severe illness profile and with psychiatric hospitalizations. Atypical antipsychotics are more likely the medications to be switched to. Finding an effective treatment option that stabilizes the disease and reduces hospitalizations will help patients and payers as well.