OBJECTIVES: To assess the cost-effectiveness of olanzapine long-acting injection (OLAI) compared with risperidone long-acting injection (RLAI) for patients with schizophrenia in Norway. METHODS: A discrete event simulation (DES) model was developed from a Norwegian healthcare system perspective to estimate the costs and outcomes associated with OLAI vs. RLAI for patients with schizophrenia over a five year period. The model focuses on patients that have been non-adherent to oral medication resulting in recurrent relapses. These patients responded to oral treatment during the stablisation phase of their illness and have been modeled as entering the maintenance phase of treatment.  DES was considered an appropriate approach due to the heterogeneous nature of schizophrenia.  Norwegian unit cost and resource utilisation data were used. Key clinical inputs were relapse rates and treatment discontinuation rates obtained from open-label studies. Occurrences of side-effects, such as post-injection syndrome, were accounted for. Cost and outcomes included direct medical costs and quality-adjusted life years (QALYs) discounted at a rate of 4%.  A range of deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Results were analysed over a 5-year time horizon. OLAI was found to be dominant over RLAI.  Incremental costs and outcomes were -63,323 NOK (-€7,085) and 0.07 QALYs.  OLAI was associated with fewer relapses (1.41 vs. 1.81 for RLAI) and a longer time on treatment (3.98 years vs. 3.69 years for RLAI).  Base case results were most sensitive to changes in the relapse and treatment discontinuation rates, the cost of relapse, and the time horizon.  Probabilistic results confirmed OLAI’s dominance over RLAI.    CONCLUSIONS: The economic evaluation indicates that OLAI is highly cost-effective compared to RLAI.  As an efficacious and well-tolerated treatment, OLAI constitutes an important maintenance treatment option for patients with schizophrenia experiencing recurrent relapse and previously struggling with adherence to oral medication.