Background: As individuals with thalidomide embryopathy now reaching their 60's they undergo long-term sequelae of their prenatal damage and experience a wide range of secondary health problems, in particular chronic musculoskeletal pain, movement restrictions, and mental disorders. These health problems are having a negative impact on their life circumstances and their health-related quality of life (HRQOL).Objective: The aim of this study was to determine the HRQOL in individuals with thalidomide embryopathy in comparison to individuals of the ageadjusted general population in Germany with and without chronic disease conditions (primary outcome). And, further explore the influence of impairment patterns, pain stage, and mental disorders on physical and mental dimensions of HRQOL (secondary outcome). Methods: A cross-sectional survey of 202 individuals with thalidomide embryopathy from North Rhine-Westphalia/Germany was conducted, which gathered information about physical examinations including a standardized determination of the pain stage, a structured psychological interview, and the HRQOL. The final dataset was 186 cases for primary outcome. Results: Individuals with thalidomide embryopathy (50.6 years, 55.9% females) show a significantly reduced physical HRQOL comparison to the ageadjusted German population with chronic diseases (physical component score;