Indiana University-Purdue University Indianapolis (IUPUI) / Little is known regarding the psychosocial outcomes of adult siblings of adults with autism. Accordingly, the current study sought to: (1) illuminate factors that predict health-related quality of life, caregiver burden, and reported benefits in adult siblings of adults with autism, using a stress and coping framework and (2) compare outcomes of siblings of adults with autism (n = 31) to siblings of adults with Down syndrome (DS) (n = 54). For the within subject hypotheses, analyses were repeated within the DS group and an overall Disability group (n = 97). The Disability group consisted of participants in the Autism and Down syndrome groups plus twelve individuals in a mixed group of adult siblings of adults with DS who presented with co-morbid symptoms of autism. Variables were organized using The Adult Sibling Caregiver Conceptual Model (ASCCM) into three categories: antecedents (e.g., sibling relationship quality, problem behaviors of the disabled sibling), mediators (e.g., coping strategies, cognitive appraisal types), and psychosocial outcome variables (i.e., mental and physical health-related quality of life, caregiver burden, and reported benefits). For the within subject primary hypotheses, I posited a series of relationships between the antecedents and outcomes based on prior literature on demographic and individual difference predictors (e.g., siblings of adults with autism with fewer problem behaviors would have increased health-related quality of life [HRQOL], decreased caregiver burden, and increased reported benefits) and on stress and coping factors related to the burden of providing care for an individual with autism (e.g., greater use of avoidant coping strategies would be related to lower HRQOL, increased caregiver burden, and decreased reports of benefits). Exploratory hypotheses also were examined (e.g., being married would be associated with increased HRQOL, decreased burden, and increased reported benefits). The within-subject results indicated support for eight of the ten primary hypotheses and five of the six exploratory hypotheses when examined within at least one of the study groups: Autism, DS, or Disability. Overall, sibling caregivers, regardless of their sibling’s disability, reported more favorable psychosocial outcomes when demands were lower (e.g., less severe levels of problem behaviors, fewer autism symptoms exhibited by their disabled sibling, decreased additional pile-up stress), when resources were available to cope with stress (e.g., social support, respite care), and when healthy responses to stress were reported (e.g., use of emotion focused vs. avoidant coping strategies, use of challenge vs. threat appraisal types). Of note, reported benefits, which have rarely been examined in the autism literature, were strongly related to the quality of a sibling relationship across all study groups, and with the helpfulness of received services and perceived social support within the Autism group. The between subject hypotheses also were largely supported. As expected, compared to siblings of those with Down syndrome, siblings of those with autism demonstrated greater levels of caregiver burden and lower mental HRQOL. Moreover, there was a rank ordering in levels of caregiver burden across disability groups; siblings of adults with DS reported the lowest burden, siblings of adults with DS with symptoms of autism reported significantly higher levels of burden, and siblings of those with autism reported the most burden. The results imply that autism, either alone or co-morbid with another diagnosis, presents an increased risk of stress and caregiver burden, not only in parent caregivers, but also in sibling caregivers. Interestingly, there was also evidence for higher levels of stress related growth within the Autism group compared to the DS group. Future research will be needed to generalize the results of this study to broader samples of adult siblings while taking a life course perspective to assess changes in non-disabled siblings’ outcomes over time.