Objective: to evaluate the health results and the related costs of the antipsychotic medications available on the market, with emphasis on olanzapine, in outpatients with schizophrenia in naturalistic settings. Methods: 572 outpatients with schizophrenia (CIE-10 or DSM-IV) who began or changed to an oral antipsychotic medication were enrolled in blocks of 10 patients: 5 for olanzapine and 5 for other antipsychotics (AP) different to Olanzapine, according to the prescription at that time. The risk behaviors, the level of functioning, and the quality of life were analyzed with the EUROQOL-EQ-D5 scale and the Visual Analogue Scale. The use of health resources was also evaluated. The analysis compared the group that received olanzapine with the subgroups which received risperidone and typical antipsychotics (AT) in monotherapy. Results: similar percentages of suicide attempts, alcohol abuse/dependence and arrests were found in the three treatment groups. The rates of hostile and aggressive behavior were statistically lower with olanzapine vs TA (p = 0.0003). Olanzapine and risperidone proved superior in improving/ maintaining a high level of social, work and housing status vs. TA. Olanzapine and risperidone showed better results in the 5 items of EQ-5D vs. TA but only olanzapine achieved a statistical difference vs. TA in self-care, daily activities and absence of anxiety/ depression. A higher percentage of patients on olanzapine continued with the medication up to the three year endpoint (p < 0.0001 olanzapine vs TA); discontinued treatment less due to problems of efficacy or intolerability (p = 0.0005 olanzapine vs TA and p < 0.0001 olanzapine vs. TA respectively); had the lowest rates of hospitalization. Conclusions: olanzapine and risperidone were superior to the typical antipsychotics in improving the overall functioning of the patients which can be interpreted as greater and better social reintegration. The state of health and the quality of life improved with both atypicals but only olanzapine was statistically superior to the typicals. The patients on olanzapine remained in treatment for the longest period and abandoned treatment less due to problems of efficacy or intolerability. Less patients on olanzapine needed hospitalization and outpatient consultations versus typical medications which could mean savings in direct costs of the illness. ©INNN, 2007.