Introduction The aim of this controlled study was to analyze the degree and localization of 3-dimensional (3D) facial asymmetry in adult patients with cleft lip and palate (CLP) compared with a control group and its impact on the visual perception of faces. Methods The degree of 3D asymmetry was analyzed with a novel method without landmarks in 18 adults with complete unilateral CLP and 18 adults without congenital anomalies. Furthermore, the CLP and control faces were rated for appearance, symmetry, and facial expression by 30 participants. Results The results showed that adults with CLP had significantly greater asymmetry in their facial soft tissues compared with the control group. Moreover, the lower face, and particularly the midface, had greater asymmetry in the CLP patients. The perceptual ratings showed that adults with CLP were judged much more negatively than those in the control group. Conclusions With sophisticated 3D analysis, the real morphology of a face can be calculated and asymmetric regions precisely identified. The greatest asymmetry in CLP patients is in the midface. These results underline the importance of symmetry in the perception of faces. In general, the greater the facial asymmetry near the midline of the face, the more negative the evaluation of the face in direct face-to-face interactions.