OBJECTIVES: To assess changes in cost and effectiveness parameters following switch from risperidone to olanzapine during the long-term treatment of schizophrenia patients. METHODS: Patients were participants in a randomized, open-label, 1-year cost-effectiveness trial of olanzapine, risperidone, and typical antipsychotics in the treatment of schizophrenia. Study protocol permitted antipsychotic switching when clinically warranted. Resource utilization was systematically abstracted from medical records. Treatment outcomes were assessed with standard psychiatric measures. Statistical analyses assessed changes from pre-to-post switch among patients who were randomized to risperidone, but later switched to olanzapine for any cause. RESULTS: Sixty of the 218 (27.5%) patients randomized to risperidone switched antipsychotics – with 43 (72%) switching to olanzapine. Average duration on risperidone before switching to olanzapine was 86.1 days (mean maximum dose 4.5 mg/day). Most of these switchers (86%) completed the 1-year study on olanzapine (average maximum dose 13.3 mg/day). Following switch to olanzapine, patients experienced significant improvements on clinical and social parameters (both, p<0.001), with 35.7% of the prior non-remitters achieving remission status. Mean total daily costs changed from $49.5/day pre-switch, to $44.4/day post-switch (non-significant difference). CONCLUSIONS: Olanzapine appears to be a cost effective ²rescue² option for patients who require switching from risperidone in the long-term treatment of schizophrenia.