OBJECTIVES: As a chronic illness, schizophrenia consumes a vast amount of healthcare resources and is therefore associated with both high direct and indirect healthcare costs. Pervasive suboptimal quality of life coupled with a high economic burden renders policy and healthcare decision makers seeking cost-effective treatments. This study aimed at evaluating the cost-effectiveness of aripiprazole once-monthly 400mg (AOM) versus paliperidone palmitate 50-150mg (PP) in the maintenance treatment of schizophrenia based on the QUALIFY study (NCT01795547). METHODS: QUALIFY was a 28-week, randomised, open-label, rater-blinded study comparing AOM with PP in the maintenance treatment of schizophrenia. Two key outcomes demonstrated improvements for AOM vs. PP: Heinrichs-Carpenter Quality of Life Scale (QLS) and Clinical Global Impression – Severity (CGI-S). To assess cost-effectiveness, minimal clinically important differences (MCIDs) were sought from the literature in the respective assessment scales. Treatment response was defined as a change from baseline to study termination of at least 6 points and 1 point on QLS total score and CGI-S score, respectively. Mean treatment specific costs (incl. drug acquisition) were estimated using QUALIFY healthcare resource utilisation data. The analysis was conducted from a UK perspective considering direct costs only.  RESULTS: In the deterministic analysis mean total costs per-patient were £2,093 and £2,954 for AOM and PP, respectively (p<0.001). According to the QLS MCID, 49% of patients receiving AOM were classified as responders vs