OBJECTIVES: The functional status of individuals and their self-rated quality of life has been shown to be an important predictor of general quality of life, mortality, and utilization of health services. We investigated the factors associated with physical function (PF) and general health (GH) at baseline in patients with prostate cancer as well as factors associated with changes over the course of disease. METHODS: Data from CaPSURE, a longitudinal disease registry of men with prostate cancer, was used to identify a group of men who were newly diagnosed with prostate cancer, have defined initial treatment, and had one pre-treatment and at least two years of post- treatment HRQOL assessments. HRQOL were measured by SF-36 and were assessed bi-annually. Changes in PF and GH scores over time were evaluated by mixed model analysis, accounting for type of treatment received, time of HRQOL assessment, age at diagnosis, level of function at baseline, and education level. RESULTS: 3625 patients met the study criteria. At baseline high level of physical functioning and general health (median 95 and 75 respectively) were demonstrated. In multivariate mixed model analysis type of treatment, baseline level of physical function, time of HRQOL assessment, age, education level, and interaction term between time and type of treatment were significantly associated with changes in PF and GH over time. Differences in PF and GH persisted through the period of study and varied greatly depending on level of function at baseline (adjusted means 62.7 vs. 95.2 for PF and 62.1 vs. 78.0 for GH at first year after treatment). CONCLUSION: Further evaluation of the relationship between GH and PF can provide us with important information to identify critical elements of HRQOL. Identification of the specific determinants of perceived and objective measure could provide us with tools for improving overall quality of life in patients with prostate cancer.