Purpose The World Health Organization Quality of Life Scale Brief Version (WHOQOL-BREF) is used for patients with schizophrenia although no validation is available. This work addresses this issue by dealing with its psychometric properties in a clinical sample of patients with schizophrenia. Methods Two hundred forty-one patients from 10 Adult Mental Health Care Centers (AMHCC) meeting the following inclusion criteria were included: (1) International Classification of Diseases-10 or ICD-10 diagnosis of schizophrenia, (2) Global Assessment of Functioning scores or GAF ≤ 50, 3) Illness duration of more than 2 years and (4) Clinical stability at assessment time. Patients were evaluated at baseline and at one-year follow-up regarding quality of life (QOL), clinical variables and other psychosocial measures. Results Internal consistency was excellent for the total WHOQOL-BREF (0.88 at baseline and 0.89 at follow-up) and adequate (0.65-0.78 at baseline; 0.66-0.79 at one-year follow-up) for the WHOQOL-BREF domains. Correlations between WHOQOL-BREF scores and those of global functioning, psychiatric symptoms, disability and social support ranged between small and large. There were significant differences between groups of patients with schizophrenia in the WHOQOL-BREF. Patients who were anxious, disabled, lacked social support and used more social services scored significantly lower in some or all WHOQOL-BREF domains. Changes in WHOQOL-BREF scores were positively associated with changes over time in global functioning, social support and use of health services, and negatively with psychiatric symptoms and disability (correlation coefficients between small and moderate). After one-year follow-up, patients improved in overall functioning and there was a decrease in psychiatric symptoms. Conclusions This study shows that the WHOQOL-BREF has good reliability and validity, and suggests that it is suitable for the assessment of QOL in patients with schizophrenia.