BACKGROUND: Data on health-related quality of life (HRQoL) changes among Americans aged 65 following colorectal cancer (CRC) diagnosis and treatment are limited. This study compared HRQoL changes among CRC patients across stages from before to after diagnosis with matched noncancer controls. METHODS: This population-based study used the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey (MHOS) data set (1998-2007). Medicare Advantage beneficiaries diagnosed with CRC between their baseline and follow-up MHOS (n5349) were matched to noncancer controls (n51745) using propensity scores. Mixedeffects analysis of covariance models estimated changes in HRQoL (measured by the Medical Outcomes Study Short Form-36/Veterans RAND 12-item Survey) and the ability to perform 6 activities of daily living (ADLs) between baseline and follow-up. Logistic regression models estimated odds ratios for ADL impairments and major depressive disorder (MDD) risk. RESULTS: Mean time between CRC diagnosis and follow-up MHOS was 12.369.8 months. Compared with controls, CRC patients had significantly lower scores in all physical and mental health domains at follow-up. The greatest decrements were observed in physical health and were largely driven by declines in the 6 months postdiagnosis and in stage III and IV patients. At follow-up, CRC patients had greater overall ADL impairment and difficulty with dressing, eating, and getting in/out of chairs. CRC patients, particularly stage IV patients, had greater odds of being at risk for MDD relative to controls. CONCLUSIONS: This study further underscores the adverse effects of CRC on physical health and the need to support older Americans' basic self-care needs, with attention to later-stage patients' increased debility.