OBJECTIVES: To evaluate 12 months cost-effectiveness of risperidone long-acting injection (RLAI) in patients with schizophrenia enrolled in the electronic-Schizophrenia Treatment Adherence Registry (e-STAR) from Czech Republic. METHODS: e-STAR is an international long-term, prospective, observational study in patients with schizophrenia who commenced RLAI treatment (based on SmPC indication criteria). Analyzed data covered one year of retrospective (prior to RLAI initiation) and 12 months of prospective observation. A total of 156 patients have completed the 12 months prospective period. Assessed costs were: hospitalisation (duration and frequency), antipsychotic medication and co-medication all from the payer’s perspective in 2007 prices. Efficacy parameters included GAF (Global Assessment of Functioning) and CGI-S (Clinical Global Impression-Severity) scores. RESULTS: Mean annual costs per patient increased form €2361 in the retrospective period to €4695 during the prospective observation. Mean cost drivers were hospitalisation (60.6 % of total medical retrospective costs) and antipsychotic medication (89.2 % of total medical prospective costs). Costs of RLAI could not be offset by significant reductions in hospitalization (both frequency and duration per event) and co-medication. Improvements in GAF (47.6 vs. 71.1) and CGI (4.78 vs. 3.16) scores resulted in incremental cost-effectiveness ratios of €960 to €1440 per improvement by 1 category of clinical significance (1 point for CGI and 10 points for GAF). CONCLUSIONS: Switching to risperidone long-acting injection in patients with treatment failure, non-compliance or intolerance of current antipsychotic medication is cost-effective despite higher costs of antipsychotic medication. The analyses yield incremental cost-effectiveness ratios fall below commonly accepted willingness to pay thresholds.