Antipsychotic discontinuation rates are a powerful indicator of medication effectiveness in schizophrenia. We examined antipsychotic discontinuation in the Schizophrenia Outpatient Health Outcomes (SOHO) study, a 3-year prospective, observational study in outpatients with schizophrenia in 10 European countries. Patients (n=7728) who started antipsychotic monotherapy were analyzed. Medication discontinuation for any cause ranged from 34% and 36% for clozapine and olanzapine, respectively, to 66% for quetiapine. Compared to olanzapine, the risk of treatment discontinuation before 36 months was significantly higher for quetiapine, risperidone, amisulpride, and typical antipsychotics (oral and depot), but similar for clozapine. Longer medication maintenance was associated with being socially active and having a longer time since first treatment contact for schizophrenia, whereas higher symptom severity, treatment with mood stabilizers, substance abuse, having hostile behaviour were associated with lower medication maintenance. Antipsychotic maintenance in SOHO was higher than the results of previous randomized studies.