Zuclopenthixol and haloperidol are antipsychotic medications displaying different galenic forms, while risperidone is available on the market only in tablet form. The depot form presents advantages; the duration of action allows 3-4 weeks between administrations. A meta-analysis showed that zuclopenthixol patients had a higher response rate than haloperidol. A Markov model was developed to estimate the cost-effectiveness of the three antipsychotics in schizophrenia over a 5-year period. Model parameter estimates were based on a meta-analysis and literature. The viewpoint was that of the French National Health Insurance. When compared to haloperidol and risperidone, zuclopenthixol patients had additional 4 and 7 months without relapse correspondingly over a 5-year period. The estimated 5-year medical cost associated with zuclopenthixol was 800 and 1100 euros less than haloperidol and risperidone, respectively, per patient. Sensitivity analyses indicated that the results were robust to changes in key variables. The model indicates that the zuclopenthixol treatment strategy dominates haloperidol and risperidone.