Continuity is a key treatment success factor to reduce relapse and hospitalisation rates of schizophrenic patients. Atypical antipsychotics with daily oral administration are associated with improved efficacy, tolerability and compliance compared with older, conventional neuroleptics. Similarly, conventional depots have shown to reduce the risk of relapse over oral conventional. The novel long-acting risperidone, administered intramuscularly once every two weeks, is the first long-acting formulation of an atypical antipsychotic. OBJECTIVES: To assess the cost-effectiveness of long-acting risperidone versus oral olanzapine and haloperidol decanoate in recently diagnosed schizophrenic patients. METHODS: A cost-effectiveness analysis is considered. Main assumption is that compliance improvement, thanks to a long-acting formulation leads to an increased efficacy. A decision tree model was built with a time horizon of 2 years. A French payers perspective was adopted. Outcome probabilities and cost estimates were based on published data, and supplemented with expert opinion. Only direct medical costs were considered. Effectiveness measures were relapse-free patients and patients maintained on the same treatment for 2 years. RESULTS: 76,30% of the patients receiving long-acting risperidone remained relapse-free, compared with 69,60% with olanzapine and 47,70% with haloperidol decanoate. Of the patients treated with long-acting risperidone, 82.7% remained successfully on treatment for 2 years, compared with 74.80% and 57.30% for patients treated with olanzapine and haloperidol decanoate respectively. Total direct cost per patient over 2 years were €13168 with risperidone, €13280 with olanzapine, and €16910 with haloperidol decanoate. Long-acting risperidone was the dominant strategy in each case and remained dominant strategy in sensitivity analyses. CONCLUSION: The model indicates that treatment with long-acting risperidone reduces relapses, improves continuity of treatment, and is associated with decreased total direct medical costs over two years, when compared with oral olanzapine and haloperidol decanoate.