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Background: Most survivors of colorectal cancer (CRC) are older adults who are at high risk of experiencing adverse effects and decreased health-related quality of life (HRQOL) related to cancer and its treatments., Objective: This study aimed to describe HRQOL and the demographic and clinical factors associated with HRQOL among older adult, long-term survivors of CRC., Methods: A sample of older adult, long-term survivors of CRC (N = 14 458) from the Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey dataset was selected. Hierarchical multiple regression was used to analyze the contribution of demographic and clinical variables to HRQOL as measured by the Veterans Rand 12-item scale., Results: The mean respondent age was 79 years with an average time from diagnosis to survey being about 13 years. In the final model, gender, race, education, income, previous radiation treatment, cardiovascular disease, inflammatory bowel disease, depression, pain, fatigue, functional status, and general health perception were all significantly correlated with mental HRQOL (R2 = 0.53). For physical HRQOL, age at diagnosis, race, marital status, education, time since diagnosis, comorbid conditions, depression, pain, fatigue, functional status, and general health perception were all significant correlates (R2 = 0.85). Symptoms were the largest contributors to mental and physical HRQOL, accounting for 43% and 50% of the variance, respectively., Conclusion: Pain, depression, and fatigue significantly affect the HRQOL of older adult survivors of CRC, underscoring the need for long-term survivorship care., Implication for Practice: Aggressive symptom assessment and management may be key to improving the HRQOL in this population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)