OBJECTIVES: To investigate the cost-effectiveness of aripiprazole compared to standard-of-care (SOC) in the Schizophrenia Trial of Aripiprazole (STAR). METHODS: STAR was a multi-centre, 26-week, randomised, naturalistic, open-label study comparing aripiprazole with SOC (defined as clinician’s choice of olanzapine, quetiapine or risperidone) in the management of community-treated patients with schizophrenia (1). The primary outcome in the cost-effectiveness analysis was the cost per unit of improvement on the main clinical outcome in STAR, the Investigator’s Assessment Questionnaire (IAQ) (2). Secondary outcome measures were the cost per additional CGI-I responder and the cost per unit of improvement on the Quality of Life Scale (QLS). Data on service use and employment were collected alongside the trial. Statistical adjustment was made for baseline characteristics on all outcomes. The perspective taken was that of the NHS and social care in the UK. RESULTS: Aripiprazole was associated with a significantly better improvement on the IAQ (p=0.0002), the CGI-I response rate (p=0.0080) and the QLS scores (p=0.0003) as compared to SOC. The improvement observed in the QLS scores at six months in this study approached that of clinical significance at 1 year (3.4). The incremental cost effectiveness ratio (ICER) for the IAQ was £714 per unit of improvement. We estimated that a clinically significant improvement would be an 8 point improvement in the IAQ score. The cost per 1% increase in the number of CGI-I responders was £1413. Thus it would cost £1413 to go from 10 to 11 responders in a sample of 100 patients. The ICER for the QLS suggests a cost of £288 for each unit of improvement gained. CONCLUSIONS: Aripiprazole has shown to provide improvements in effectiveness and quality of life at a reasonable cost compared to SOC based on an economic analysis of a naturalistic trial.