OBJECTIVE: Although schizophrenia is a common and disabling medical condition, little is known about its impact on health-related quality of life (HRQoL) in Asians. We therefore characterized HRQoL in outpatients with schizophrenia in Singapore, and identified factors that influenced HRQoL in these patients. METHODS: A consecutive sample of outpatients with schizophrenia seen in the Institute of Mental Health in Singapore completed a standardized English or Chinese questionnaire containing the Schizophrenia Quality of Life Scale (SQLS), the Short Form 36 Health Survey (SF-36) and the Health Utilities Index Mark 3 (HUI3) classification system. Patients were assessed for psychiatric symptoms using a standard checklist, and socio-economic and clinical variables were collected through patient interviews and data extraction from medical records. Subjects' SF-36 scores were compared with adjusted Singaporean population norms. Factors influencing HRQoL measured by these instruments were identified using stepwise multiple linear regression models. RESULTS: Two hundred two outpatients with schizophrenia completed survey questionnaires (English-speaking: n = 140). Mean (SD) age of the subjects was 37.8 (10.2) years, and 52% were female. The majority of the subjects were ethnic Chinese (83.7%). The mean (SD) duration of schizophrenia was 8.4 (7.4) years, and 30.7% of subjects reported hospitalization in a psychiatric ward in the 3 months preceding the survey. Mean SF-36 scores of the subjects were 4.7 to 37.2 points lower than adjusted Singaporean population norms (p <0.01 for all comparisons, one-sample t-tests). Better HRQoL in these subjects (in stepwise regression models) was associated with less psychiatric symptoms, increasing age and duration of illness, less years of education, presence of chronic medical conditions and usage of English questionnaires. CONCLUSIONS: Outpatients with schizophrenia in Singapore experienced clinically important reductions in HRQoL; both disease related and other variables influenced HRQoL in these patients.