OBJECTIVES: To analyse effectiveness of flupentixol compared to other first and second generation antipsychotics for the treatment of schizophrenia in routine care.  METHODS: A retrospective cohort study was conducted using administrative data from four sickness funds with a combined number of 12.6 million insured. Patients discharged from hospital with an ICD-10 diagnosis of schizophrenia in 2003 were followed for 12 months. Rehospitalisation during follow-up was analysed using a hurdle regression model. Differences in treatment costs, defined as cost of pharmaceutical and cost of inpatient care, were analysed assuming a gamma distribution for treatment costs and using a log-link-function. To control for possible confounding, the models adjusted for age, gender, and prior hospitalisations due to schizophrenia in 2000, 2001 and 2002. RESULTS: A total of 8610 insured were included, of which 177 treated with flupentixol during follow-up, while 429 and 2284 were treated with other first and second generation antipsychotics, respectively. Compared to patients treated with flupentixol (predicted hospitalisation for the average patient: 19 days), predicted hospitalisation did not differ significantly for patients treated with other first (16.9 days, p=0.0919) or second generation antipsychotics (19.5 days, p=0.1418). Predicted treatment costs for the average patient (age=41.5 years, male, prior hospitalisation 26.7 days per year) were €4384 if treated with flupentixol, €7021 if treated with an other first generation antipsychotic, and €6819 if treated with a second generation antipsychotic. Differences in treatment costs between first and second generation antipsychotics increased with severity.  CONCLUSIONS: The effectiveness of flupentixol preventing relapse in patients with schizophrenia appears to be similar to that of other first and second generation antipsychotics. However, the low treatment costs for patients treated with flupentixol might be explained by the small number of patients who were hospitalised (70 insured) and the larger share of patients treated with its depot formulation.