ObjectiveThe purpose of the study was to compare antipsychotic monotherapies in terms of time to discontinuation in a sample of schizophrenia patients followed-up for 36months. MethodsTwo hundred and twenty schizophrenia patients, treated with antipsychotic monotherapy and followed-up in psychiatric outpatient clinics of Universities of Milan and Utrecht were included in the study. A survival analysis (Kaplan-Meier) of the 36-month follow-up period was performed to compare the single treatment groups. End-point was considered as discontinuation of treatment for recurrence, side effects or non-compliance. ResultsPatients treated with haloperidol discontinued more than the other groups (Breslow: risperidone p<0.001, olanzapine p<0.001, quetiapine p=0.002, clozapine p<0.001, aripiprazole p=0.002). Lack of efficacy (recurrence) was a more frequent reason for discontinuation in the haloperidol group than in the olanzapine group (p<0.05). Extrapyramidal side effects (EPS) were more frequent in the haloperidol group than with olanzapine (p<0.05). The olanzapine group presented more frequently weight gain than the other groups, without reaching statistical significance. ConclusionsPatients treated with atypical antipsychotics appear to continue pharmacotherapy longer than patients treated with haloperidol. In addition, atypical antipsychotics seem to be more protective against recurrences than haloperidol. However, these results should be cautiously interpreted in the light of potential confounder factors such as duration of illness. Copyright (c) 2016 John Wiley & Sons, Ltd.