Understanding medical factors that influence quality of life for men with prostate cancer is an important goal. This study analysed the relationship between cancer stage and quality of life, including measures of physical and psychological well-being. A secondary analysis of data from 341 ambulatory men with prostate cancer. The Functional Assessment of Cancer Therapy (FACT)-Prostate version, Urinary Function Subscale of UCLA Prostate Cancer Index, and Hospital Anxiety and Depression Scale (HADS), were administered during their clinic visit. Stage of disease and treatment history was obtained from clinic records. Patients were categorized into localised (T1-T2, N0, M0, n=186), locally advanced (T3-T4, N0, M0, n=92), and metastatic (T3-T4, N1-3 or Ma-c, n=63) disease. Differences in quality of life based on stage were examined using multivariate analyses controlling for age, treatment type, time since diagnosis, co-morbidities, and urinary function. Stage of prostate cancer was significantly associated with most FACT scales (Physical, Functioning, Social) and summary scores (Treatment Outcomes Index, FACT total score). However, no significant associations were observed between stage of cancer and psychological symptoms of depression or anxiety. This association remained significant even after controlling for the influence of illness co-morbidity, urinary functioning, time since diagnosis, age, and type of treatment. Higher cancer stage appears to be associated with poorer quality of life in prostate cancer and this association does not appear to be simply a function of the symptoms and disability that accompany advanced disease. These results have implications for understanding the impact of progression of prostate cancer on patients' health-related quality of life.