Autistic adults frequently show increased physical or mental health conditions and impairments in social, occupational, and other life domains. Accordingly, they often report reduced health-related quality of life. Yet, numerous barriers prevent effective healthcare for autistic adults. To date, the impact of healthcare barriers on health-related quality of life in autism has not been investigated. We, thus, sought to investigate the health-related quality of life of autistic adults without intellectual disability in Germany and analyze previously reported and novel predictors of health-related quality of life including healthcare barriers using multiple linear regression. Within a nationwide online survey, 311 autistic adults completed the Short-Form Health Survey and the Barriers to Healthcare Checklist. Demographic, clinical, and healthcare-related predictors were also assessed. Participants showed below-average mental and significantly reduced physical health-related quality of life compared to a German normative sample. Several independent variables differentially predicted mental and physical health-related quality of life. Healthcare barriers resulted as the only predictor, which explained variations in both domains: the more barriers autistic adults experienced, the lower their mental and physical health-related quality of life. Barriers emerged as the strongest predictor for mental health-related quality of life. Our results raise awareness for the barriers autistic adults experience in getting appropriate healthcare and the possible consequences for the individual. Improved healthcare access might contribute to better health-related quality of life in autism.