This study examined the relationship between self-determination and perceived quality of life for youth and young adults with chronic conditions and disabilities over time. A total of 34 individuals completed the Life Satisfaction Index–Adolescents and the Arc’s Self-Determination Scale at study baseline and again 1 year later. Controlling for perceived quality of life at baseline and other relevant health and demographic variables, linear regression analysis was performed to examine the longitudinal relationship between self-determination and perceived quality of life. Self-determination was significantly associated with two subdomains of quality of life over time. Those individuals with higher self-determination at baseline reported higher perceptions of satisfaction with both personal development and personal fulfillment 1 year later. Findings suggest that there may be a relationship between self-determination and specific subdomains of perceived quality of life for youth and young adults with chronic conditions and disabilities that extends over time. Studies using larger international samples followed over a longer period of time are required to substantiate these findings.