OBJECTIVES: Frequency of adverse events -AEs- related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. A pharmacoeconomic model has been developed to ascertain the economic impact of patients experiencing these AEs. The purpose of this study was to model the economic consequences of AEs related with current antipsychotics in Spain. METHODS: A cost-effectiveness model was developed using a Markov modeling approach simulating treatment of a cohort of schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. The model assumes equivalent efficacy among the antipsychotics. Conditional probabilities of developing any of four adverse events was calculated. Treatment was modified (decrease dose, switch medication) according to incidence of AEs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a 3rd party payer perspective (only direct medical cost are computed). Results are shown as annual cost per month with psychotic symptoms controlled. Univariate sensitivity analysis was performed. RESULTS: The therapeutic strategy starting with Ziprasidone showed the most favorable cost-effectiveness ratio, being the dominant option (showing the lower costs and the greater number of months with symptoms controlled), versus the other options considered. The annual cost per patient per month with symptoms controlled was €1.035 with that of ziprasidone, versus €1.084, €1.087, and €1.090 with haloperidol, risperidone and olanzapine, respectively. Results are robust to one-way sensitivity analysis. CONCLUSIONS: Adverse events related with the usage of antipsychotic drugs produce a considerable economic impact. Availability of drugs with similar effectiveness but better tolerability than existing agents, should positively impact on clinic aspects of schizophrenia and health care budgets as well.