© 2018 American Psychological Association. Disorders/differences of sex development (DSD) refer to congenital conditions with atypical sex development and are associated with psychosexual issues. The aim of this study was to assess body image and self-esteem across the DSD spectrum and to study the impact of diagnosis and mediating characteristics. Method: Data collection was part of dsd-LIFE, a cross-sectional study conducted by 14 European expert clinics on wellbeing and health care evaluation of adults diagnosed with DSD. Main outcome measures in the present analyses were the Body Image Scale and Rosenberg Self-Esteem Scale. Additional data were obtained on treatments, openness, body embarrassment, sexual satisfaction, anxiety, and depression. Results: The participating sample (n = 1,040) included 226 classified as Congenital Adrenal Hyperplasia, 225 as Klinefelter Syndrome, 322 as Turner Syndrome, and 267 as conditions with 46,XY karyotype. Many participants had received hormonal and surgical treatments. Participants scored lower on body image and self-esteem compared to control values, whereas each diagnosis showed different areas of concern. Limited openness, body embarrassment, and sexual issues were frequently reported. Overall body satisfaction was associated with BMI, hormone use, openness, body embarrassment, anxiety, and depression; genital satisfaction with age at diagnosis, openness, sexual satisfaction, and body embarrassment. Body embarrassment, anxiety, and depression predicted lower self-esteem. Conclusions: While each DSD showed specific issues related to body image and self-esteem, our findings indicate that the related factors were similar across the conditions. Clinical care on this subject could be improved by giving specific attention to factors like openness, body embarrassment, sexuality, anxiety, and depression.