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BACKGROUND Fatigue is prevalent and distressing among cancer survivors, but its subjective nature makes it difficult to identify. Fatigability, defined as task-specific fatigue, and endurance performance may be useful supplemental measures of functional status in cancer survivors. METHODS Fatigability, endurance performance, and cancer history were assessed every 2 years in Baltimore Longitudinal Study of Aging participants between 2007 and 2015. Fatigability was defined according to the Borg rating of perceived exertion scale after a 5-minute, slow treadmill walk; and endurance performance was calculated according to the ability and time to complete a fast-paced, 400-meter walk. The association between cancer history, fatigability, and endurance performance was evaluated using longitudinal analyses adjusted for age, sex, body mass index, and comorbidities. RESULTS Of 1665 participants, 334 (20%) reported a history of cancer. A combination of older age (>65 years) and a history of cancer was associated with 3.8 and 8.6 greater odds of high perceived fatigability and poor endurance, respectively (P < .01). Older adults with and without a history of cancer walked 42 and 23 seconds slower than younger adults without a history of cancer, respectively (P < .01). The median times to the development of high fatigability and poor endurance were shorter among those who had a history of cancer compared with those who had no history of cancer (P < .01). CONCLUSIONS The current findings suggest that a history of cancer is associated with fatigability and poor endurance and that this effect is significantly greater in older adults. Evaluating the effects of cancer and age on fatigability may illuminate potential pathways and targets for future interventions. Cancer 2018;124:1279-87. © 2018 American Cancer Society.