We tested whether health related quality of life (HRQOL) predicts mortality, development of active cytomegalovirus (CMV) disease, and study retention. We studied 957 patients with CD4 counts <100 cells/mm 3 in AIDS Clinical Trials Group Protocol 204, a randomized, double-blind trial comparing three prophylactic regimens against CMV end-organ disease. The MOS-HIV, a brief HRQOL questionnaire, generated physical health summary (PHS) and mental health summary (MHS) scores. We used Cox proportional hazards to predict events by baseline HRQOL, adjusted for treatment, demographics, and CD4. Each point increase in baseline PHS decreased the risk of death by 4%, CMV by 2%, and dropout by 2%. Each point increase in baseline MHS decreased the risk of death by 4% and study dropout by 1%. In conclusion, self-rated physical and mental health demonstrated predictive validity for survival, CMV end-organ disease, and retention in advanced HIV patients. The results show the clinical importance of HRQOL and may facilitate interpretation by clinicians.