Objective: To assess the cost-effectiveness of olanzapine orally dissolving tablets (ODT) and olanzapine standard oral tablets (SOT) during the usual treatment of schizophrenia patients from a U.S. health care perspective. The model also compared olanzapine ODT with other antipsychotics in SOT and ODT formulations. Methods: Published medical literature, unpublished data, and a clinical expert panel were used to populate a one-year micro-simulation model comparing olanzapine ODT with olanzapine SOT, and with other antipsychotics in SOT (risperidone, quetiapine, ziprasidone, aripiprazole and perphenazine) and ODT formulations (risperidone and aripiprazole). The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, health care resource utilization and associated costs. Key results were annual direct cost per treatment and incremental cost-effectiveness values per one inpatient relapse avoided and per one QALY gained. Results: Based on model projections, olanzapine ODT therapy was slightly more costly ($9674 vs. $9602) but more effective in terms of a lower hospitalization rate (14% vs. 16%) and better QALY (0.78 vs. 0.75) than olanzapine SOT therapy, with favorable incremental cost per inpatient relapse avoided ($2157) and QALY gained ($2454). Olanzapine ODT was more cost-effective than olanzapine SOT and also more cost-effective compared to other comparators. Conclusion: The utilization of olanzapine ODT for the treatment of schizophrenia is predicted in this model to be more cost-effective than olanzapine in standard oral tablets and more cost-effective than other comparators in either orally dissolving tablet or standard tablet formulations.