Data from the European Schizophrenia Outpatient Health Outcomes, a 3-year, prospective, observational study of health outcomes associated with antipsychotic treatment in outpatients with schizophrenia (n=10 972 enrolled), were used to assess the impact of the first switching of antipsychotic medications, with a focus on olanzapine, on clinical status and tolerability outcomes. Patients were defined as those who (1) started olanzapine at baseline and changed treatment; (2) started another antipsychotic at baseline and changed to olanzapine; and (3) changed from and to a non-olanzapine antipsychotic. A logistic regression model was used to analyse the impact of switching on treatment response and tolerability. Patients switching from olanzapine were less likely to respond than patients switching to olanzapine (OR: 0.59; 95% CI: 0.40, 0.87). Patients who switched from olanzapine and those who switched neither from nor to olanzapine were more likely to have extrapyramidal symptoms (OR: 3.79; 95% CI: 2.02, 7.10 and OR: 2.18; 95% CI: 1.23, 3.86, respectively) and loss of libido (OR: 1.89; 95% CI: 1.21, 2.96 and OR: 1.56; 95% CI: 1.04, 2.35, respectively) compared with patients who switched from another antipsychotic to olanzapine. Patients who switched to olanzapine experienced a higher weight gain. In conclusion, among patients switching antipsychotic medication, those who switched to olanzapine had better long-term outcomes.