Objective: Decisional autonomy—or sense of one’s ability to make independent choices about one��s life—is especially relevant to individuals who may feel their autonomy is limited due to physical challenges. Past work has found associations between measures of autonomy and quality of life (QoL) in individuals with disability and in older adults. However, it is less clear how decisional autonomy influences the impact of pain and fatigue severity on QoL, especially in adults aging with physical disability. This study examined the relationship of decisional autonomy to QoL and the extent to which autonomy moderates the association between symptom severity and QoL. Method: We used hierarchical linear regression models to examine the associations between autonomy, pain and fatigue, and quality of life in a sample of individuals with long-term disability. In 2 sets of models, we examined individuals reporting some level of fatigue (n = 1,060, M_age = 62.66, SD = 11.88) and some level of pain (n = 964, M_age = 62.79, SD = 11.69). Results: We found that decisional autonomy significantly predicted QoL over and above other measures related to social participation. Decisional autonomy also weakly moderated the associations between fatigue and QoL and the associations between pain and QoL. Conclusions: The findings indicate that levels of decisional autonomy may be important to QoL in individuals aging with physical limitations. (PsycINFO Database Record (c) 2019 APA, all rights reserved)