The orbital region of subjects with Down syndrome (DS) has been scanty described so far. We wanted to detail the morphologic characteristics of the soft tissue orbital region in Italian and North Sudanese subjects with DS. The three-dimensional coordinates of 10 landmarks on the orbital soft tissues were obtained using computerized anthropometry in 53 Italian and 64 North Sudanese subjects with DS aged 4 to 52 years, and in 461 (Italian) and 682 (North Sudanese) sex- and age-matched controls. From the landmarks, linear distances, ratios, areas, and angles were calculated, z scores computed, and compared by t-tests and analyses of covariance. In North Sudanese DS subjects, intercanthal width and height-to-length ratio were increased; biorbital width, eye height, length, and area were reduced. Eye fissure and orbital inclinations relative to Frankfort plane were reduced, whereas orbital inclinations versus the true horizontal were increased. In Italian DS men, orbital height and height-to-length ratio were increased, eye length was decreased; orbital inclination versus the true horizontal was increased. For almost all measurements, a significant effect of age was found. No effects of sex were found. Ethnic group influenced orbital height, area, and orbital inclination versus Frankfort plane. All paired measurements had similar discrepancies on both sides. The orbital soft tissues of North Sudanese DS subjects differed from those of their reference subjects, but this was only partially true for Italian subjects. The 2 ethnic groups had different alterations in their soft tissue orbital regions that were influenced by age, but not by sex.