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The aim in this study was to evaluate the influence of skeletal class, facial type, and sex on soft tissue thickness (STT) of the craniofacial midline in a Brazilian subpopulation. Thus, 121 cone beam computed tomography (CBCT) scans (54 males and 67 females, age 21 to 40 yrs) composed the study sample. Patients were classified according to skeletal class (class I, II, and III) and facial type (brachycephalic, mesocephalic, and dolichocephalic), and STT was measured (mm) in 10 landmarks in the craniofacial midline for each CBCT scan. Multivariate analysis of covariance evaluated facial STT with regard to multiple independent variables (sex, age - covariate, facial type, and skeletal class). TEM and rTEM assessed the intra-examiner agreement. STT was significantly greater in males than in females for all regions measured (p < 0.05), except for the pogonion-pogonion' landmark (p>0.05). In general, class III individuals had significantly thicker soft tissue in the maxilla - subspinale-subnasale', prosthion-labrale superius', and incision-stomion' regions, while class II subjects had thicker soft tissue in the infradentale-labrale inferius' mandibular landmark (p < 0.05). Regarding facial type, dolichocephalic individuals showed significantly thicker soft tissue in the supramentale-supramentale' mandibular landmark, whereas brachycephalic subjects had thicker soft tissue in maxillary regions - prosthion-labrale superius' and incision-stomion' (p < 0.05). rTEM values were below 5% for most landmarks, and all TEM values were below 1 mm. Skeletal class and facial type influence STT, showing a soft tissue compensation, with deeper soft tissue in areas with lower skeletal development, and/or where bone is positioned more posteriorly., (Copyright © 2020 Elsevier B.V. All rights reserved.)