OBJECTIVE: To examine the relationship between self-reported and clinically assessed quality of life (QoL) among participants in the U.S. Schizophrenia Care and Assessment Program (SCAP). METHODS: Data reflect measures obtained at the 12-month assessment period (n=908). Clinical instruments were the Quality of Life Scale (QLS), Montgomery-Asberg Depression Rating Scale (MADRS), Positive and Negative Symptoms Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS). Self-report data were obtained from Life Satisfaction (LifeSat) scale and Depression scale, component scales of the SCAP Health Questionnaire. Cross-sectional regression analyses were conducted. RESULTS: Correlation between the subjective and objective scale totals and component items were significant in most instances with magnitudes ranging from 0.2 to 0.6. Clinical rating of QLS was significantly and inversely impacted by PANSS (p<0.001) and MADRS (p<0.001). Unlike QLS, self-reported LifeSat was impacted by MADRS (p<0.001) and not by symptoms (PANSS). The magnitude of effect of MADRS was 38% greater on LifeSat than on QLS. Two QLS sub-scales (common objects and activities [COA] and interpersonal relations [IPR]) exhibited a significant relationship with LifeSat (p<0.01 and p<0.001, respectively). In the presence of MADRS, however, significance of clinical symptoms and QLS subscales diminished and R-squared increased. Clinically assessed depression exhibited a significant relationship (0.38; p<0.001) to self-reported depression. CONCLUSIONS: The relationship of self-report to clinical assessment is of particular interest for persons with schizophrenia given the current climate of participatory treatment planning and outcome milestone achievement. These findings demonstrate several important points: 1) participant self-reports and clinical assessments exhibit significant interrelation for both QoL and depression; 2) clinical symptoms and side effects are not important drivers of self-reported QoL; 3) level of depression is an important factor in patients' own sense of life satisfaction; and 4) depression scores exhibit a mediating effect between psychiatric symptom presentation and valuation of quality of life.