OBJECTIVES: The use of antipsychotics in the treatment of schizophrenia has changed patient connections to their surroundings, placing them in greater contact with their family and the environment in which they carry out daily activities. The purpose of this analysis of patients in the naturalistic setting was to evaluate the changes in health related quality of life (HRQL) associated with antipsychotic drug therapy and to evaluate the sensitivity of the Euroqol-5D (EQ-5D) as a tool for measuring HRQL in patients with schizophrenia. METHODS: The study included 2,128 patients with schizophrenia who were treated with olanzapine, 821 who were treated with risperidone or haloperidol, and small numbers of patients on other antipsychotics. Sociodemographic, clinical (global clinical impression, global activity evaluation scale, presence of extrapyramidal symptoms) and the EQ-5D as a generic tool for the measurement of the HRQL were included as variables. The patients were evaluated at treatment initiation and after 6 months. RESULTS: Olanzapine-treated patients showed the largest effect size on the Visual Analog Scale (VAS) (0.98) and the EQ-5D Index (EQ-I) (1.13) compared with the remaining antipsychotic drugs (0.58-0.75 for the VAS and 0.78-0.96 for the EQ-I). The olanzapine-treated group had the highest proportion of patients with an improvement, particularly in the daily activities and mood domains, and the lowest proportion of patients who worsened after 6 months of treatment. CONCLUSION: Treatment with antipsychotic drugs, especially olanzapine, improves the HRQL of patients with schizophrenia. The study also indicates that the EQ-5D is useful and sensitive tool for detecting changes in the health of patients with schizophrenia.